bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P4-07-01: Assessment of the hereditary component in 94 cancer predisposition genes to triple negative breast cancer
Authors: Ellsworth RE , Lovejoy LA , Shriver CD
Published: February 2018

Background: In women with triple negative breast cancer (TNBC) unselected for age or family history, 8-14% and 5% of patients harbor germline mutations in BRCA1 and BRCA2, respectively. Diagnosis of TNBC <60 years of age is one of the NCCN criterion for genetic testing of BRCA1 and BRCA2. The contribution of germline mutations in other cancer predisposition genes to TNBC, is, however, not well-studied.

Methods: TNBC was classified as tumors with <1% positively staining cells for ER and PR and HER2 = 0+, 1+ or 2+/not amplified. Genomic DNA was isolated from blood samples and targeted sequencing was performed using the TruSight Cancer panel (Illumina). Pathogenic mutations were identified using VariantStudio and classified as pathogenic, uncertain significance (VUS) or benign using ClinVar.

Results: 196 female patients diagnosed with TNBC 2001-2014 had genomic DNA available. Average age at diagnosis was 52.8 years (range 34.1-83.4 years). The majority of patients were of European (66%) or African (31%) American ancestry; 26% had a family history and 13% had died of disease with an average time to death of 2.81 years. Twenty-three (12%) of women with TNBC had pathogenic mutations in breast cancer genes BRCA1 (n=14), BRCA2 (n=5), PALB2 (n=1) and CHEK2 (n=3), two women had mutations in the colon cancer genes MUTYH, one had a mutation in the ovarian cancer gene BRIP1, and an additional three women had pathogenic mutations in cancer predisposition genes FANCD2, SDHB and XPC. An additional 42 women had VUS in 20 genes, including one in BRCA1 and 5 in BRCA2.

Discussion: Although the majority of pathogenic mutations in this cohort of women with TNBC were in the BRCA1 and BRCA2 genes (10%), panel testing allowed for the detection of mutations in other breast (2%), colon (1%), ovarian (1%) and other cancer (2%) predisposition genes. Panel testing thus identifies genes other than BRCA1/2 associated with increased risk of TNBC and may incidentally identify women who would benefit from enhanced surveillance for other cancers.

The opinions or assertions contained herein are the private ones of the author/speaker and are not to be construed as official or reflecting the views of the Department of Defense, the Uniformed Services University of the Health Sciences or any other agency of the U.S. Government.

Citation Format: Ellsworth RE, Lovejoy LA, Shriver CD. Assessment of the hereditary component in 94 cancer predisposition genes to triple negative 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 P4-07-01.
Abstract P4-08-01: Not presented
Authors: Howell A , Harkness E , Fox J , Astley S , Wiseman J , Eriksson M , Wilson M , Warren R , Hall P , Cuzick J , Evans G
Published: February 2018

This abstract was not presented at the symposium.
Abstract P4-09-04: Withdrawn
Authors: Lonning PE , Helwa R , Birkeland EE , Yates LR , Wedge DC , Lokkevik E , Eikesdal HP , Stratton MR , Campbell PJ , Knappskog S
Published: February 2018

This abstract was withdrawn by the authors.
Abstract P4-10-18: Medismart-Oncosmart: A low-cost private initiative to improve health care access in the middle-income country of Costa Rica. Overview of the breast cancer screening program
Authors: Wiernik A , Lami Casaus L , Durman M , Herrera Guido R
Published: February 2018

Background: Costa Rica is a middle-income country in Central America with a public, government run, universal health care system which provides coverage to over 95% of the population. Despite being recognized as one of the best health care systems in Latin America, recent national reports suggest that up to 15% of the population is currently on a waiting list for a medical visit or procedure. The impact of the national breast cancer screening program is unknown as the country's health care system and the national cancer registry fail to report statistical variables like screening waiting lists, breast screening coverage, stage at diagnosis, time from screening to biopsy, breast cancer subtypes, breast cancer mortality by stage, among others.

Methods: In 2014, the private health plan Medismart partnered with the private Hospital Metropolitano network with the mission of developing a low-cost health care system that provides efficient access and affordable health care services to its affiliates. Medismart's health care plan costs $12 a month per member ($6 per additional affiliated family member) and uses a copay model for health care services utilized by its beneficiaries. In 2016, Oncosmart, a program of Medismart, was developed with the goal of implementing population based screening, diagnostic procedures, cancer treatment, and survivorship care to its members. The program has no restrictions on pre-existing conditions.

Results: From January 2015 to April 2017, Medismart subscribed 50,122 members. During the first 12 months of launching the breast screening program, 3634 women (32% of target population of 11058 women over 40 years old) underwent breast cancer screening mammography, breast ultrasound or both at the Hospital Metropolitano network. The copayment price of mammography screening for Medismart members is $26 and the copayment price for breast ultrasound screening is $38. Of the women who underwent screening in this period, 153 required a breast biopsy and all biopsies performed at the Metropolitano hospital were completed within 30 days from the abnormal imaging study.

Conclusion: Medismart-Oncosmart is a low cost and efficient private initiative that improves access to breast cancer screening in Costa Rica.

Citation Format: Wiernik A, Lami Casaus L, Durman M, Herrera Guido R. Medismart-Oncosmart: A low-cost private initiative to improve health care access in the middle-income country of Costa Rica. Overview of the breast cancer screening program [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 P4-10-18.
Abstract P4-11-03: Not presented
Authors: Ryser MD , Liu Y , Hendrix L , Hyslop T , Hwang ES
Published: February 2018

This abstract was not presented at the symposium.
Abstract P4-11-04: Talking about risk in the context of GEomic profiling tests (TARGET)
Authors: Fallowfield LJ , Jenkins VA
Published: February 2018

Background: Risk of recurrence scores from genomic profiling tests such as OncotypeDX® and EndoPredict® are being used increasingly with other clinico-pathologic features to help determine the likely benefit of adjuvant chemotherapy in early stage breast cancer. Decision-making requires the balancing of likely absolute benefits in terms of preventing recurrence versus the treatment related side effects. Health literacy and numeracy skills in the general population are often poor thus explaining risk and uncertainty can be confusing especially when set against a backdrop of fear and anxiety. As clinicians are facing more of these types of conversations with their patients we developed an educational program to help when discussing genomic test results.

Methods: The development of the educational package followed discussions with key clinicians who routinely used genomic profiling tests, clinician-scientists and a review of the risk literature. We mapped out the difficulties they encountered when explaining high, intermediate and low risk test results together with the added challenges faced when communicating with patients with different personality and socio-educational characteristics. As clinicians and their patients may both have a measurable intolerance to uncertainty this may contribute irrespective of the recurrence score (RS) to seemingly irrational decisions about treatment. We rehearsed simulated patients (actors) experienced in improvisation to create different characters and filmed unscripted genomic test result consultations with cancer clinicians. This process proved successful in previous educational initiatives aimed at improving communication about clinical trials. (Jenkins et al 2006; Fallowfield et al 2012).

Results: The educational package comprises an interview with Professor Mitch Dowsett explaining the science behind gene expression profiling tests, a lecture on the psychology of risk with group exercises and strategies on how to communicate together with 5 filmed scenarios with a timecoded facilitator handbook. The scenarios depicted are based on real clinical situations and demonstrate some of the issues discussing RS with low risk patients who nevertheless wish to have chemotherapy as well as high risk patients who are averse to chemotherapy.

Conclusion: Discussions about the logic and rationale behind different treatment recommendations for breast cancer have become increasingly complex. Clinicians need an increased repertoire of communication skills to explain risks and benefits. We are now evaluating the efficacy of TARGET prior to training facilitators to roll the program out.

Citation Format: Fallowfield LJ, Jenkins VA. Talking about risk in the context of GEomic profiling tests (TARGET) [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 P4-11-04.
Abstract P4-12-13: Comparative analysis of costs between subcutaneous formulation of trastuzumab versus intravenous formulation from the perspective of the Instituto Oncológico Nacional of Panamá from January to December 2016
Authors: Martin C , Alcedo J , Araúz E
Published: February 2018

Objective: Because there is actually availability of both Intravenous(IV) and subcutaneous(SC) formulation of Trastuzumab for use in the public sector in the Instituto Oncológico Nacional and knowing that de SC formulation has been compared previously with the IV in term of efficacy in and it was not inferior and also is prefered by patients it is useful to count with a study of costs minimization that can determine what formulation results more convenient to maintain available for use in the Instituto Oncológico Nacional based on the criteria of efficiency of the intervention.(1)(2)

Methodology: This is a cost minimization study considering the cost of the treatment, the supplies and the time utilized by Pharmacy and Nursing to prepare and administer it.

Results: In relation to the cost of the treatment the SC presentation has a cost per patient 17% less than the IV presentation in relation to the cost that offers the Pharmaceutical company, considering a weight of 70 kg per patient ( IV presentation) and a fixed dose of 600 mg(SC presentation). Considering the supplies utilized by Pharmacy and Nursing to prepare and administer the IV and SC presentation, the SC presentation requires less supplies and this facilitates its administration and decreases the cost of the treatement in a 67%. In terms of time invested in preparing and administering the IV and the SC formulation, accounting for both, nursing and pharmacy, it is observed that the SC formulation requires less amount of time than the IV formulation and this decreases the cost of the treatment in a 90%.

Analisis of Saving by Use of SC Trastuzumab vs IV TrastuzumabItemSC TrastuzumabIV Trastuzumab% SavingTreatment10,578,0538,826,89417%Nursing Supplies18,9662,50387%Pharmacy Supplies31,98217,02047%Nursing Time71,7916,33591%Pharmacy Time2,28971669%Total anual cost10703081885346717%

Conclusion: With the use of the SC formulation of Trastuzumab there is combined savings of 17%, that represents anually 5985 USD per patient based on a treatment of 18 cycles of Traztuzumab per year, that results in a total saving of 1,84 million USD per year.

(1) Pivot et al. Lancet Oncol 2013 Sep;14(10):962-70.

(2)Ismael G et al. Lancet Oncol 2012 Sep;13(9):869-78

Citation Format: Martin C, Alcedo J, Araúz E. Comparative analysis of costs between subcutaneous formulation of trastuzumab versus intravenous formulation from the perspective of the Instituto Oncológico Nacional of Panamá from January to December 2016 [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 P4-12-13.
Abstract P4-13-08: Robotical-assisted laparoscopy for latissimus dorsi flap harvesting in breast reconstruction : A 23 consecutive cases report
Authors: Houvenaeghel G , Rua S , Franké O , Cohen M , Lambaudie E
Published: February 2018

Background : Latissimus dorsi (LD) flap is a classic and usual procedure for immediate or secondary breast reconstruction with good results and poor complication rate. The principal issue is the long and often painful dorsal scar. The feasibility of laparoscopic LD flap harvesting and more recently robotically-assisted laparoscopy were described in short series. We report in this article the largest series of robotically-assisted laparoscopic LD flap harvesting. We describe its feasibility and the immediate and early post operative outcomes.

Material et methods : Between January 27th and December 21th of 2016, we performed 23 robotically-assisted laparoscopic LD flap harvestings in immediate and secondary breast reconstruction. Every patient was systematically sent for an evaluation of aesthetic result, pain and satisfaction on the second, the sixth and the twelth month.

Results : 78,3% of surgeries were realized for infiltrative breast cancer.17 (73,9%) LD flaps were harvested in immediate reconstruction after nipple or skin sparing mastectomies (NSM -34,8%-or SSM -43,5%). The global mean operative time was 360,1 minutes, including bilateral and robotically-assisted mastectomies.

The mean hospital stay duration was 5 days (2-8 days).

We described one failure for secondary LD flap reconstruction (infection). The other cases resulted in successful reconstructions without heavy complications.

Discussion :Our series is the largest reported. It confirms the feasibility of a robotically-assisted procedure in breast reconstruction with LD flaps. Our study describes a reliable option for LD flap breast reconstruction without any additional scar. Some procedures were combined in selected patients with a robotic NSM with a single axillar incision.

Citation Format: Houvenaeghel G, Rua S, Franké O, Cohen M, Lambaudie E. Robotical-assisted laparoscopy for latissimus dorsi flap harvesting in breast reconstruction : A 23 consecutive cases report [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 P4-13-08.
Abstract P5-03-09: Breast cancer promotion by IL-6-mediated cross-talk between human preadipocyte and breast dutal carcinoma in situ
Authors: Kim HS , Jung M , Choi SK , Moon WK
Published: February 2018

While the role of adipocyte, one of the major components of the breast microenvironment, has been well documented in breast cancer progression, the preadipocytes function to favor early-stage breast cancer progression at the molecular level is not fully elucidated. To delineate the role of human preadipocyte (hPreAd) on breast cancer progression, we investigated a cross-talk between human breast dutal carcinoma in situ (DCIS) and hPreAd in in vivo culture and in vivo tumor model. On Co-culture system with DCIS cell line MCF10DCIS.com and primary hPreAd, proliferation, migration and invasion of MCF10DCIS.com was promoted by hPreAd. Conditioned medium (CM) of hPreAd activated signaling molecules (AKT1, ERK1/2, mTOR, FAK and STAT3) in MCF10DCIS.com. hPreAd expressed fibroblast specific protein 1 (FSP1) and alpha-smooth muscle actin (α-SMC), and increased IL-6 secretion by co-culture or MCF10DCIS.com CM, whereas adipocyte differentiation of hPreAd was suppressed by co-culture. A neutralizing antibody (NAb) of IL-6 or IL-6 receptor suppressed the MCF10DCIS.com proliferation and migration enhanced by co-culture of hPreAd. In xenograft tumor model, tumor growth of MCF10DCIS.com was enhanced by co-injection with hPreAd. IL-6 NAb had minimal effect in xenografts with MCF10DCIS.com alone; however, in models co-administered with hPreAd, IL-6 NAb had more potent effects on tumor inhibition. Taken together, our study suggests that IL-6-mediated cross-talk between preadipocyte and breast DCIS can exert the breast cancer progression at early-stage. Deciphering the cellular and molecular mechanisms behind the preadipocyte-breast DCIS crosstalk might provide new targets for improving diagnosis/prognosis and for the design of innovative therapeutic strategies.

Citation Format: Kim HS, Jung M, Choi SK, Moon WK. Breast cancer promotion by IL-6-mediated cross-talk between human preadipocyte and breast dutal carcinoma in situ [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 P5-03-09.
Abstract P5-07-02: Not presented
Authors: Sun W , Xu X-E , Jiang Y-Z , Shao Z-M
Published: February 2018

This abstract was not presented at the symposium.
Abstract P5-07-09: Identification of miRNA biomarkers for early diagnosis of basal-like breast cancer
Authors: Wong CK , Thiagalingam S
Published: February 2018

The routine screening for breast cancer relies primarily on imaging techniques such as mammography and ultrasonography, but it is often not sensitive enough for early detection and requires complementary approaches. Recent studies suggest that microRNAs (miRNAs) could be used as biomarkers for breast cancer due to its relative stability in archived formalin-fixed tissues as well as in bodily fluids. However, the identity of unique miRNAs that could discriminate proliferative and malignant states of the disease has remained elusive. Since TGFβ-induced epithelial-mesenchymal transition (EMT) represents a critical step during tumor progression and intravasation, studying the cancer cell at the mesenchymal state and its precursor could help to identify these critical diagnostic biomarkers. To identify novel biomarkers for early detection, we performed miRNA gene expression profiling of an established basal-like breast cancer (BLBC) model system with and without disruption of TGFβ signaling. We have identified a panel of miRNAs, including miR-210-3p, that are highly expressed in the motile, mesenchymal stage, which could potentially be used as markers in liquid biopsies for early detection of invasive BLBC. Conversely, we also found some miRNAs, including miR-200c and miR-4417, highly expressed in the noninvasive, epithelial stage. Transient overexpression of miR-4417 in mesenchymal BLBC cells was able to suppress migration and mammosphere formation in vitro, suggesting that it could block progression of BLBC, a disease highly prevalent in young African-American women and lacks targeted therapy.

Citation Format: Wong CK, Thiagalingam S. Identification of miRNA biomarkers for early diagnosis of basal-like 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 P5-07-09.
Abstract P5-07-12: miR-34a as a prognostic biomarker for overall survival triple negative breast cancer within Tunisian patients
Authors: Medimegh I , Ayari H , Baraudi O , Majoul H , Omrane I , Yousef E , Benayed F , Benromdhan K , Gaboury L , Mader S , Benammarelgaaied A
Published: February 2018

Introduction: miR-34a has been recently introduced to clinical trials especially in breast cancer depending on its crucial role as microRNA suppressor tumors since it regulates several oncogenes. We explore here the prognostic effect of miR-34a on triple negative breast cancer (TNBC) overall survival compared to no triple negative (NTNBC) group and its effect on PARP-1 and BRCA1 protein expression.

Methods: 76 patients with TNBC and NTNBC were recruited for this study. miR-34a was quantified using qPCR Syber Green technique. PARP-1 and BRCA1 were analyzed by IHC using Tissue Micro-Array method.

Results: PARP-1 is more expressed in TNBC compared to NTNBC; P = 0.04; RR= 1.8 (1.1-3.1), however, BRCA1 is less expressed in TNBC; P = 0.03; RR= 2 (1.2-12.6).

Furthermore, we evaluated the relationship between miR-34a and clinicopathological features with survival rate of both studied groups, we found that miR-34a is more expressed among patients with distance metastases in TNBC group P = 0.001; RR = 6.5 (2.1-19.6).

Survival analysis showed that miR-34a low expression in TNBC was remarkably related to overall survival; P=0.012. Furthermore, multivariate survival test suggested that the absence of miR-34a was linked to the poor survival within TNBC according to the presence of distance metastasis; P=0.048; HR= 2.69. Our results showed that miR-34a is decreased in triple negative breast cancer patients with a very poor prognosis.

Conclusion:Our results give mechanistic insights in miR-34a as a prognostic biomarker for overall survival Triple Negative Breast Cancer within Tunisian patients through its effect on PARP-1 and BRCA1 protein expression which may open potential new strategies towards prevention and therapeutic inhibition of PARP-1 positive within mammary tumors.

Citation Format: Medimegh I, Ayari H, Baraudi O, Majoul H, Omrane I, Yousef E, Benayed F, Benromdhan K, Gaboury L, Mader S, Benammarelgaaied A. miR-34a as a prognostic biomarker for overall survival triple negative breast cancer within Tunisian patients [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 P5-07-12.
Abstract P5-12-04: The impact of bariatric surgery on mammographic breast density
Authors: Hosseini A , Khoury AL , Carter J , Wong JM , Alvarado MD , Ewing C , Esserman LJ , Mukhtar RA
Published: February 2018

Background:

Bariatric surgery decreases breast cancer risk, but its impact on mammographic findings is not well understood. Obesity and breast density both increase breast cancer risk, but paradoxically are inversely related. We investigated how mammographic density changes after bariatric surgery, and whether or not that change is related to amount of weight loss.

Methods:

We reviewed records for 349 prospectively collected patients who underwent bariatric surgery between 2013-2015, and identified 45 women with pre- and post-operative screening mammograms within 1.5 years of surgery. We recorded body mass index (BMI), Breast Imaging-Reporting and Data System density, and calculated excess BMI loss. Data were analyzed in Stata 14.2.

Results:

Average age was 54 years, mean pre-operative BMI was 44 (range 36-72), and mean percentage excess BMI lost was 73% at 1.3 years. One third had a change in mammographic breast density, which increased 93% of the time (p<0.001). Amount of weight loss was not associated with density change; in fact, weight loss was lower in those with a density change than in those without a density change (68% versus 75% excess BMI lost).

Conclusions:

The majority of women with a mammographic change had an increase in breast density, despite bariatric surgery being associated with reduced breast cancer risk. Interestingly, the amount of weight loss was not associated with change in breast density. These findings suggest the metabolic effects of bariatric surgery have an effect on breast cancer risk independent of BMI reduction. Future work will include studying mammographic changes associated with non-surgical weight loss.

Citation Format: Hosseini A, Khoury AL, Carter J, Wong JM, Alvarado MD, Ewing C, Esserman LJ, Mukhtar RA. The impact of bariatric surgery on mammographic breast density [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 P5-12-04.
Abstract P5-15-03: Withdrawn
Authors: Demark-Wahnefried W , Rogers L , Fruge A , Grizzle W , Tsuruta Y , Azrad M , Oelschlager D , Oster R , Krontiras H
Published: February 2018

This abstract was withdrawn by the authors.
Abstract P5-21-26: T-DM1 activity in metastatic HER2-positive breast cancer patients who have received prior trastuzumab and pertuzumab: NSABP B-005
Authors: Tiwari SR , Sussman T , Kota K , Moore HC , Montero AJ , Budd GT , Puhalha S , Abraham J
Published: February 2018

Background :

The pivotal phase III EMILIA trial reported a progression free survival (PFS) rate of 9.6 months and an objective response rate of 43% with T-DM1 in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane. However, there is very limited data on the efficacy of T-DM1 in patients who have received prior pertuzumab either neoadjuvantly or as first line therapy in the metastatic setting. The primary goal of this study was to assess the clinical efficacy (tumor response rates and median duration on therapy) of T-DM1 in patients previously treated with pertuzumab and trastuzumab.

Methods:

After IRB approval, a cancer data registry and electronic pharmacy database were utilized to identify breast cancer patients receiving treatment with T-DM1 at Cleveland Clinic and University of Pittsburgh. Patients that received trastuzumab and pertuzumab, in either the neoadjuvant or metastatic setting, with baseline and follow up imaging available for review were identified. Patient charts were reviewed to collect accurate information about the treatment sequencing and outcomes. RECIST version 1.1 was utilized for tumor assessment and patients with measurable disease and non measurable disease were included in the study.

Results:

We identified a total of 23 patients with a median age of 55 years that met the inclusion criteria. 69% percent of patients received T-DM1 as first line or second line therapy and 31% received it as third line or later. All patients had at least 1 measurable lesion. Best overall response showed rates of complete response, partial response and stable disease of 17%, 26% and 22% respectively. 35% patients progressed on first assessment after start of treatment. The median duration on therapy was 5.3 months (range 3 weeks to 33 months) with 43% of patients receiving T-DM1 for greater than 6 months.

Conclusion:

Our results were comparable to those reported by EMILIA trial. T-DM1 has reasonable clinical efficacy in patients who have received prior treatment with pertuzumab and trastuzumab with an overall response rate of 43% and median duration on therapy of 5.3 months.

Citation Format: Tiwari SR, Sussman T, Kota K, Moore HC, Montero AJ, Budd GT, Puhalha S, Abraham J. T-DM1 activity in metastatic HER2-positive breast cancer patients who have received prior trastuzumab and pertuzumab: NSABP B-005 [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 P5-21-26.
Abstract P5-22-04: Efficacy of thoracic paravertebral block for reducing acute post-mastectomy pain
Authors: Herazo-Maya F , Egurrola J , Restrepo CE , Torres L , Palacios L , Ossa CA , Borrero M , Angel GA , Marquez JJ , Valencia S , Perez A , Oyola JC , Lobo L , Gomez R , Garcia H
Published: February 2018

Background: Mastectomy is associated with acute and chronic postoperative pain. This study investigated the efficacy of thoracic paravertebral block (TPB) compared to local anesthetic of surgical wound (LASW) in breast cancer patients undergoing mastectomy.

Methods: This phase 3, randomized controlled, single blind, parallel arms and superiority clinical trial aimed to evaluate the efficacy of TPB compared to LASW on acute pain at rest and motion at 24 hours post-mastectomy, measured by a visual analog scale (VAS). The study size of 60 patients is determined to have 90% power to detect a difference of 20% in acute pain in favor of TPB. In TPB group use of ultrasound was mandatory to guide puncture of intervertebral space T3 for infiltrating 0.5% bupivacaine at dose of 1.5 mg/kg. In LASW group was used bupivacaine 0.5% at dose of 1.5mg/kg on subcutaneous tissue of surgical area. VAS was used to measure surgical pain at rest and motion in 2,4,6,12 and 24 hours post-operatives for both groups. Trial Registry: ClinicalTrials.gov; Identifier:NCT02609321.

Findings: From 08-2015 to 09-2016, 60 breast cancer patients were enrolled; 3 dropped off consent. Mean age was 51 year; 78% had stage II and III; and 65% receive neoadjuvant chemotherapy.There were no significant differences in the VAS pain measurement for the groups of BWT compared to LASW in the 24 hour measurement, neither at rest (P=0.6525) nor in movement (P=0.7929). There were no significant differences in both groups for repeated pain measurements (5 measures mean), total dose of opioid administration, time to first dose of opioids or adverse events.

Conclusions: There were not statistical differences for post-mastectomy acute pain in first 24 hours between TPB and LASW patients. According our findings the use of TPB should not routinely recommended for breast cancer patients undergoing mastectomy.

Citation Format: Herazo-Maya F, Egurrola J, Restrepo CE, Torres L, Palacios L, Ossa CA, Borrero M, Angel GA, Marquez JJ, Valencia S, Perez A, Oyola JC, Lobo L, Gomez R, Garcia H. Efficacy of thoracic paravertebral block for reducing acute post-mastectomy pain [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 P5-22-04.
Abstract P5-22-18: Withdrawn
Authors: Cohen M , Benhaim S , Chauvet M-P , Penault-Llorca F , Bertrand P , Giraud S , Opinel P , Faure C , Meynard P , Charafe E , Houvenaeghel G
Published: February 2018

This abstract was withdrawn by the authors.
Abstract P5-23-05: Prognostic value of PD-L1 expression in male breast cancer
Authors: Abdeljaoued S , Bettaieb I , Adouni O , Goucha A , Chiba D , Bouzaiene H , Ben Hassouna J , Boussen H , Rahal K , Gamoudi A
Published: February 2018

Background

Growing evidence have shown promise for targeting programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) signaling in several tumors. In female breast cancer, PD-L1 expression has been correlated with poor clinical outcome. However, whether PD-L1 has any indication for prognosis in male breast cancer (MBC) patients remains unknown. The purpose of this study was to examine the expression levels of PD-L1 in MBC and to identify the relationship between PD-L1 expression and patient survival.

Methods

We retrospectively identified 110 male breast cancer patients diagnosed between 2000 and 2013 at Salah Azaïz Cancer Institute. PD-L1 expression was evaluated by immunohistochemistry (IHC) using CD274 antibody. Specimens were scored as IHC low or high, when < 5% or ≥ 5% of cells were PD-L1 positive, respectively. The association between expression of PD-L1 and survival was investigated using Kaplan-Meier survival and COX proportional hazard regression analyses.

Results

Median follow up was 12.5 months [range 1-132 months]. High expression of PD-L1 was observed in 64.5% of MBC samples (71/110). PD-L1 expression was significantly associated with advanced clinical stage (p=0.012), higher histological grade (p=0.014), higher Ki67 expression (p=0.023) and hormone-receptor negative status (p=0.024). Patients with high PD-L1 expression had significantly shorter overall survival (OS) than patients with low expression (p=0.002, hazard ratio (HR) =5 [2.624–10.642]). Multivariate analysis identified PD-L1 as an independent prognostic factor for OS (p<0.001, HR = 0.775 [0.680–0.870]).

Conclusion

Our results indicate that high PD-L1 expression may be a prognostic indicator for reduced OS. Thus, PD-L1 expression is a promising novel biomarker with prognostic significance in MBC and may suggest a potential therapeutic target of anti-PD-L1 antibody therapy in MBC patients.

Citation Format: Abdeljaoued S, Bettaieb I, Adouni O, Goucha A, Chiba D, Bouzaiene H, Ben Hassouna J, Boussen H, Rahal K, Gamoudi A. Prognostic value of PD-L1 expression in male 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 P5-23-05.
Abstract P6-03-08: Detection ability of dedicated breast positron emission tomography for small-sized breast cancer
Authors: Sueoka S , Masumoto N , Nishina M , Kimura Y , Suzuki E , Goda N , Sasada S , Kajitani K , Emi A , Haruta R , Kadoya T , Kataoka T , Okada M
Published: February 2018

Background: Whole body (WB) 18F-fluorodeoxyglucose positron emission tomography (PET) has a relatively poor spatial resolution (>1 cm), which limits the capability to detect small lesions. Therefore, small-sized breast cancers (≤1 cm) may not be visible on WBPET. To overcome these limitations, dedicated breast PET (DbPET) has been developed to improve spatial resolution. DbPET enables detailed high-resolution images within the breast. We aimed to determine whether DbPET can detect small-sized breast cancer compared to WBPET.

Methods: We investigated 203 consecutive patients (217 tumors) (T1–3, N0–3a, M0) with breast cancer who underwent concurrent DbPET and WBPET between January 2016 and March 2017. All DbPET and WBPET images were semi-quantified based on standard uptake values. The diagnostic performance of each scanner was assessed in DbPET and WBPET. Tumors were classified based on pathological classification as follows: Tis, ductal carcinoma in situ (DCIS); T1a, ≤0.5 cm; T1b, 0.5–1 cm; and T1c, 1–2 cm; T2, 2–5 cm; T3, >5 cm. The sensitivities of DbPET and WBPET were compared in each size group.

Results: Table 1 shows the detection rate of breast cancer in WBPET and DbPET

The detection rate of breast cancer in WB- and Db-PET DbPETWBPETpTumor sizeDetection (-) n(%)Detection (+) n(%)Detection (-) n(%)Detection (+) n(%) Tis6(14.6)35(85.4)18(43.9)23(56.1)0.0030T1a2(8)23(92)7(28)18(72)0.0594T1b2(6.5)29(93.5)10(32.3)21(67.7)0.0077T1c5(8.2)56(91.8)11(18)50(82)0.1038T20(0)57(100)1(1.8)56(98.2)0.2375T30(0)2(100)0(0)2(100)-total15(6.9)202(93.1)47(21.7)170(78.3)<0.0001

. The overall detection rate in DBPET [93.1% (202/217)] was significantly higher than that of WBPET [78.3% (170/217)] (P < 0.001). For smaller tumors, DbPET was more sensitive than WBPET: Tis (85.4% vs. 56.1%), T1a (92% vs. 72%), T1b (93.5% vs. 67.7%), T1c (91.8% vs. 82%), T2 (100% vs. 98.2%), and T3 (100% vs. 100%). The sensitivity of DbPET was significantly higher than that of WBPET in Tis (P = 0.003) and T1b (P = 0.008) and tended to be higher than that of WBPET in T1a (P = 0.059). Conversely, no significant differences were observed in T1c (P = 0.103) and T2 (P = 0.238).

Conclusion: The imaging sensitivity of DbPET was higher than that of WBPET. DbPET showed significant sensitivity in DCIS and tumors ≤1 cm, which is a weak point for WBPET. DbPET may serve as a new diagnostic modality to detect small-sized breast cancer.

Citation Format: Sueoka S, Masumoto N, Nishina M, Kimura Y, Suzuki E, Goda N, Sasada S, Kajitani K, Emi A, Haruta R, Kadoya T, Kataoka T, Okada M. Detection ability of dedicated breast positron emission tomography for small-sized 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 P6-03-08.
Abstract P6-05-01: Interactions between adipocytes and breast cancer cells stimulate cytokine production and drive Src/SOX2/miR-302b mediated malignant progression
Authors: Picon-Ruiz M , Pan C , Drewes-Elger K , Jang K , Besser A , Zaho D , Morata-Tarifa C , Kim M , Ince TA , Azzam D , Wander S , Cote RJ , Guy HA , El-Ashry D , Torne-Poyatos P , Marchal JA , Slingerland JM
Published: February 2018

Consequences of the obesity epidemic on cancer morbidity and mortality are not fully appreciated. Obesity is a risk factor for many cancers, but the mechanisms by which it contributes to cancer development and patient outcome have yet to be fully elucidated. Here, we examined the effects of coculturing human-derived adipocytes with established and primary breast cancer cells on tumorigenic potential. We found that the interaction between adipocytes and cancer cells increased the secretion of proinflammatory cytokines. Prolonged culture of cancer cells with adipocytes or cytokines increased the proportion of mammosphere-forming cells and of cells expressing stem-like markers in vitro. Furthermore, contact with immature adipocytes increased the abundance of cancer cells with tumor-forming and metastatic potential in vivo. Mechanistic investigations demonstrated that cancer cells cultured with immature adipocytes or cytokines activated Src, thus promoting Sox2, c-Myc, and Nanog upregulation. Moreover, Sox2-dependent induction of miR-302b further stimulated cMYC and SOX2 expression and potentiated the cytokine-induced cancer stem cell-like properties. Finally, we found that Src inhibitors decreased cytokine production after coculture, indicating that Src is not only activated by adipocyte or cytokine exposures, but is also required to sustain cytokine induction. These data support a model in which cancer cell invasion into local fat would establish feed-forward loops to activate Src, maintain proinflammatory cytokine production, and increase tumor-initiating cell abundance and metastatic progression. Collectively, our findings reveal new insights underlying increased breast cancer mortality in obese individuals and provide a novel preclinical rationale to test the efficacy of Src inhibitors for breast cancer treatment.

Citation Format: Picon-Ruiz M, Pan C, Drewes-Elger K, Jang K, Besser A, Zaho D, Morata-Tarifa C, Kim M, Ince TA, Azzam D, Wander S, Cote RJ, Guy HA, El-Ashry D, Torne-Poyatos P, Marchal JA, Slingerland JM. Interactions between adipocytes and breast cancer cells stimulate cytokine production and drive Src/SOX2/miR-302b mediated malignant progression [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 P6-05-01.
Abstract P6-07-05: Interactions between adipocyte stem cells and normal or tumoral mammary epithelial cells. Potantial role of BRCA status and estrogen pathway
Authors: Benderra M-A , Zaoui M , Atlan M , Ferrand N , Denis JA , Leban M , Lamari F , Larsen AK , Sabbah M , Gligorov J
Published: February 2018

Prophylactic mastectomies are more and more frequent. As a result, breast reconstruction is also more frequent and mammary lipofilling often used to improve the aesthetic results. Contradictory cliniacal data have been published concerning the risk of breast cancer after using this technique. It is possible that Adipose-Derived Stem / Stromal Cells (ADSC or ASC), present in the lipofilling may interact with normal or tumoral epithelial mammary cells.

In this context, we studied the effect of conditioned media of human ASC on different tumor breast lines (MCF7, T47D, ZR75-1, SKBR3, SUM159). The ASCs were extracted from non-cancer patients with identical body mass index (BRCA1 and BRCA2 mutated or wild-type).

We observed that the conditioned media of ASC induced the proliferation of luminal, Her2 and basal-like tumor breast lines. This proliferative effect is more important when ASCs are differentiated and the BRCA mutation status has no impact on it. Finally, we have demonstrated an estrogen signaling within the ASCs which is set up during their differentiation. Differentiated ASCs express ERα and produce 17β-estradiol (E2). This estrogenic pathway seems to be established independently of the BRCA mutational status. The proliferative effect on luminal mammary lines induced by conditioned media of ASC could pass through this estrogenic signaling, but remains to be confirmed.

These data highlight the fact that adipose-derived stem cells in mammary lipofilling should only be used after a cancer has been eliminated, as there are still some uncertainties concerning their implication on carcinogenesis.

Citation Format: Benderra M-A, Zaoui M, Atlan M, Ferrand N, Denis JA, Leban M, Lamari F, Larsen AK, Sabbah M, Gligorov J. Interactions between adipocyte stem cells and normal or tumoral mammary epithelial cells. Potantial role of BRCA status and estrogen pathway [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 P6-07-05.
Abstract P6-07-10: The ERβ4 variant induce transformation of the normal breast mammary epithelial cell line MCF-10A; the ERβ variants ERβ2, ERβ4 and ERβ5 increase aggressiveness of TNBC by regulation of hypoxic signaling
Authors: Faria M , Karami S , Granados-Principal S , Dey P , Verma A , Choi DS , Elemento O , Bawa-Khalfe1 T , Chang JC , Gustafsson J-A , Strom AM
Published: February 2018

Triple negative breast cancer (TNBC) still remains a challenge to treat in the clinic due to a lack of good targets for treatment. Although TNBC lacks expression of ERα, the expression of ERβ and its variants are detected quite frequently in this cancer type and can represent an avenue for treatment. We show that the variants of ERβ, namely ERβ1, ERβ2, ERβ4, and ERβ5, regulate aggressiveness of TNBC by regulating hypoxic signaling. RNA-seq of patient derived xenografts (PDX) from TNBC show expression of ERβ4 and ERβ5 variants in more than half of the samples. Furthermore, expression of ERβ4 in the immortalized, normal mammary epithelial cell line MCF-10A that is resistant to mammosphere formation caused transformation and development of mammospheres. By contrast, ERβ1, ERβ2 or ERβ5 were unable to support mammosphere formation. We have previously shown that all variants except ERβ1 stabilizes HIF-1α but only ERβ4 appear to have the ability to transform normal mammary epithelial cells, pointing towards a unique property of ERβ4. We propose that ERβ variants may be good diagnostic tools and also serve as novel targets for treatment of breast cancer.

Citation Format: Faria M, Karami S, Granados-Principal S, Dey P, Verma A, Choi DS, Elemento O, Bawa-Khalfe1 T, Chang JC, Gustafsson J-A, Strom AM. The ERβ4 variant induce transformation of the normal breast mammary epithelial cell line MCF-10A; the ERβ variants ERβ2, ERβ4 and ERβ5 increase aggressiveness of TNBC by regulation of hypoxic signaling [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 P6-07-10.
Abstract P6-08-15: Not presented
Authors: Chen M , Sun H , Zhao Y , Fu W , Yang L , Gao S , Li L , Jiang H , Jin W
Published: February 2018

This abstract was not presented at the symposium.
Abstract P6-08-18: Prognostic multigene testing in breast cancer: Patterns, disparities, and opportunities for advancing standardized patient care
Authors: Bernhardt EB , Caffrey AG , Celaya MO , Celaya V , Chamberlin MD , Rees JR
Published: February 2018

Background: The decision to give adjuvant chemotherapy to patients with hormone receptor positive early stage breast cancer is controversial given the overall good prognosis with local therapy (surgery and radiation) plus hormonal therapy alone. In 2004, the 21-gene RT-PCR assay recurrence score (Oncotype) was developed to stratify early stage patients into categories of high, low, and intermediate recurrence rates considering treatment with local and hormonal therapy alone. This was incorporated into the NCCN guidelines in 2008. We sought to compare NCCN guidelines to actual practice patterns.

Methods: By retrospective review, data were examined from eight state registries participating in the National Program of Cancer Registries' Comparative Effectiveness Research program: Alaska, Colorado, Florida, Idaho, Louisiana, North Carolina, New Hampshire, and Rhode Island. These were then compared to NCCN guidelines for prognostic multigene testing.

Results: Of the 28,372 cases examined, 18.6% were classified as carcinoma in situ, 39.6% were stage I, 24.3% were stage II, 9.1% were stage III, 4.9% were stage IV, and 3.6% were unknown stage. The overwhelming majority of cases, 75.5%, were estrogen receptor (ER) or progesterone receptor (PR) positive, while 15.7% were ER and PR negative, and 8.8% were hormone receptor unknown. Approximately 40% of cases were human epidermal growth factor receptor 2 (HER2) positive, and the remaining 60% were HER2 negative or unknown. Approximately 72% of patients were node negative or had unknown nodal involvement, while the remaining 28% had at least micro-metastatic nodal disease. Invasive ductal carcinoma was the most common histology accounting for 71.4% of cases examined. Median age was 62. Data analysis for the use of prognostic multigene testing in relation to NCCN guidelines, race, age, and the above clinical factors is on-going and will be presented at SABCS 2017.

Conclusion: The purpose of this study is to examine the factors associated with the use of prognostic multigene testing according to the NCCN guidelines, including personal and clinical factors. By identifying practice patterns we can then address disparities and opportunities for advancing standardized quality patient care.

Citation Format: Bernhardt EB, Caffrey AG, Celaya MO, Celaya V, Chamberlin MD, Rees JR. Prognostic multigene testing in breast cancer: Patterns, disparities, and opportunities for advancing standardized patient care [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 P6-08-18.