bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P6-08-26: Clinical characteristics of breast cancer patients with ATM mutations
Authors: Militello Loredana , Barrera Angelica M Gutierrez , Albarracin Constance , Bedrosian Isabelle , Arun Banu K 
Published: March 2020

Abstract
Background: Pathogenic ATM gene mutations are associated with increased risk of developing several cancers such as lymphoid, gastric, breast, central nervous system, skin, and other cancers. The relative risk of breast cancer is 2.3, with a higher risk seen for women under the age of 50 years. Only few and small studies have reported on the characteristics of breast cancers in women with ATM mutations. Here, we aimed to describe the clinical and pathological characteristics of a single institution largest cohort, to the best of our knowledge, of breast cancer patients with ATM mutations.
Methods: Patients with breast cancer who presented to the University of Texas MD Anderson Cancer Center Clinical Cancer Genetics clinics and underwent genetic testing for hereditary breast cancer and were found to have an ATM mutation were included. A retrospective review of a prospectively maintained research database was performed for ATM mutation status as well as patient clinical and pathological characteristics. IRB approval was granted for this analysis.
Results: Between 2012 and 2019, a total of 4093 breast cancer patients underwent genetic testing for hereditary breast cancer that included ATM gene testing. The median age of diagnosis of breast cancer was 49.3 (17-89), and median age at genetic testing was 52.1 (18-86). 72% of patients had stage 0-III and 3.2% stage 4 disease. Among patients with ATM pathogenic mutations, 37.7% (10) versus 21.7% (843) of ATM negative patients had a history of multiple primaries of any cancers. The table below shows characteristics of ATM pathogenic mutation carriers versus ATM negative patients.
Conclusion: This is a single institution cohort of breast cancer patients with ATM mutations that show distinct clinical characteristics, such as multiple primary cancers. These findings could have therapeutic implications and should be confirmed in larger cohorts.
Pathogenic Mutation of ATM ATM NegativesVariablesn%n%ERPositive4075.5221757.1Negative11.976019.6Unknown1222.690423.3PRPositive3667.9188448.5Negative59.4107027.6Pos/Neg00.010.03Unknown1222.692623.9Her2Positive1018.958611.3Negative2241.5206257.0Unknown2139.6123314.2Stage059.43178.2I1324.597825.2II1120.8106527.4III713.243611.2IV47.51243.2Unknown1324.596124.8Nuclear GradeI23.82596.7II1935.8111228.7III1120.8115629.8Unknown2139.6135434.9Triple Negative?Yes00.053913.9No3769.8222757.4Unknown1630.2111528.7
Citation Format: Loredana Militello, Angelica M Gutierrez Barrera, Constance Albarracin, Isabelle Bedrosian, Banu K Arun. Clinical characteristics of breast cancer patients with ATM mutations [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-08-26.
Abstract P6-10-11: In vitro chemo interrogation of viable circulating tumor associated cells from breast cancer patients
Authors: Crook Timothy , Akolkar Dadasaheb , Patil Sanket , Mhase Vishakha , Patil Revati , Sims Cynthe , Datta Vineet , Apurwa Sachin , Mane Viwek , Gawai Ashok , Apastamb Madhavi , Srinivasan Ajay , Datar Rajan 
Published: March 2020

Abstract
Background: Chemoresistance in cancer cells is the underlying reason for treatment failure. Real-time monitoring of chemoresistance and response (CRR) is a fundamental but unmet prerequisite of precision oncology. Repetitive invasive biopsies to obtain tumor tissue for in-vitro CRR profiling are neither feasible nor advisable. Circulating Tumor Associated Cells (C-TACs) have been proposed for functional assessment of CRR. In this observational study, we performed CRR profiling on viable C-TACs from breast cancer patients.
Methods: In this 3 arm study, viable C-TACs were harvested from 15 ml of peripheral blood obtained from 242 breast cancer patients using CellWizard™, an epigenetically active media with paradoxical cytotoxicity that selectively kills normal cells and simultaneously confers survival benefit on cells of tumorigenic origin. C-TACs were stained with EPCAM, CK, CD45 and GCDFP. Viable Tumor Derived Cells (TDCs) harvested from freshly biopsied tumor tissue (Arm 1, N=48) and concurrently obtained C-TACs were simultaneously CRR profiled irrespective of whether patient was pre-treated or otherwise. Arm 2 (N=100) included refractory (pre-treated) patients where C-TACs were evaluated for resistance to previously administered drugs. Arm 3 (N=124) included recently diagnosed therapy naïve patients where C-TACs were evaluated for innate chemoresistance.
Results: In Arm 1, CRR profile of C-TACs showed 96.1% concordance with CRR profile of concurrently obtained TDCs. In Arm2, CRR profiling of C-TACs identified chemoresistance due to prior drug exposure in 91.4% of patients. In Arm 3, innate chemoresistance was observed in 42% of patient samples towards commonly used first / second line Standard of Care drugs belonging to various functional categories such as mitotic inhibitors, DNA damaging agents, topo inhibitors and antimetabolites.
Conclusion: This study shows for the first time the feasibility of CRR profiling of C-TACs and its correlation to in-vitro and in-vivo CRR characteristics of the tumor. Adoption of C-TAC based CRR profiling can provide unprecedented real time treatment oversight towards treatment selection and monitoring of drug resistance for personalized treatment of breast cancer patients.
Citation Format: Timothy Crook, Dadasaheb Akolkar, Sanket Patil, Vishakha Mhase, Revati Patil, Cynthe Sims, Vineet Datta, Sachin Apurwa, Viwek Mane, Ashok Gawai, Madhavi Apastamb, Ajay Srinivasan, Rajan Datar. In vitro chemo interrogation of viable circulating tumor associated cells from breast cancer patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-10-11.
Abstract P6-10-30: Developing 3D subtyping model for breast cancer patients based on absolute quantitation or ER, PR and Her2 at protein level
Authors: Zhang Jiandi 
Published: March 2020

Abstract
The concept of intrinsic subtypes of breast cancer have been well accepted with several predictor applications based on this concept achieved success in clinical practice. However, all these predictor applications are based on gene expression profiling, and the surrogate assay at protein level is based on immunohistochemistry (IHC), which is known to be associated with inherent problems of subjectivity and inconsistency. Consequently, subtyping of breast cancer patients in clinical practice is limited either by the cost or the inaccuracy (surrogate assay). In this study, we proposed the first predictor model at protein level based on the three-dimensional (3D) distribution of samples using ER, PR and Her2 protein levels as coordinates.
Method: Quantitative dot blot (QDB) method was used as a universal platform to achieve absolute quantitative of ER, PR, Her2 and Ki67 protein levels using total tissue lysates prepared from 2 × 15 um Formalin Fixed Paraffin Embedded (FFPE) slices. Total of 1248 FFPE slices were provided from local hospitals sequentially and non-selectively. The measured tissue biomarker levels were plotted in 3D scatterplot for analysis, in combination with provided clinicopathological parameters and overall survival data.
Results: We observed natural segregation of these samples into three distinct groups to mimic “balls falling from ceiling corner” distribution pattern. This distribution pattern disappeared when the scatterplot was narrowed in a small box of ER&lt;0.2 nmole/g, PR &lt;0.8 nmole/g and Her2&lt;0.3 nmole/g. When the observed Her2 level at 0.3 nmole/g was used as cutoff to convert samples dichotomously, we achieved overall concordance with IHC at 94.8%. In addition, 260 out 271 Her2 positive samples were either with ER&lt;0.2 nmole/g or PR&lt;0.8 nmole/g or both, with 8 more samples at the vicinity of corner group. The model was further evaluated with both the overall recurrence and survival of the patients.
Conclusion: We developed the first 3D predictor model for subtyping of breast cancer patients based on the absolute and quantitative levels of ER, PR and Her2 at protein level. We propose this model the projection of intrinsic types at protein level. The adoption of this predictor model in clinical practice should significantly lower the barrier to allow practicing subtyping of breast cancer patients in daily clinical practice worldwide.
Citation Format: Jiandi Zhang. Developing 3D subtyping model for breast cancer patients based on absolute quantitation or ER, PR and Her2 at protein level [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-10-30.
Abstract P6-13-07: Cost-effective care for newly diagnosed breast cancer patients: Think globally, act locally
Authors: Tang Annie , Ugarte Shannon , John Rohan , Khoury Amal , Knopf Kevin 
Published: March 2020

Abstract
Conscientious use of scarce health economic resources allows for social distributive justice by avoiding over-treatment of patients to allow for appropriate treatment for a broader patient population. Lower socioeconomic status patients with breast cancer have a worse outcome compared to higher socioeconomic status patients in the United States. In part, this is due to poor access to medical care and a failure of logistical care. We implemented a community based breast cancer multidisciplinary program with weekly meetings to discuss patients, coordinate care, and provide cost-effective care to a medically under-served and vulnerable patient population. Breast surgery and medical oncology providers saw patients together in a co-located space and expedited timely initiation of neoadjuvant and adjuvant chemotherapy / hormone therapy for appropriate patients. The conjoint clinic allowed for rapid temporal integration of care in our safety net hospital / community. A single breast cancer navigator provided rapid identification of patients, coordination through clinics, and assistance with social work and other needs. Weekly 30 minute discussion sessions reviewing all new and relevant follow up patient issues were implemented in lieu of a breast cancer tumor board for efficiency. The relevant published clinical literature was reviewed on an ongoing basis. Cost-effective care was obtained by implementing: 1) avoidance of post lumpectomy radiation for selected patients based on PRIME2 trial results, 2) judicious use of post-mastectomy radiation based on a careful re-analysis of the data, 3) avoidance of adjuvant/neoadjuvant Perjeta in HER2+ patients based on a lack of overall survival, 4) adoption of 6 month schedule of adjuvant Herceptin, 5) avoidance of excessive imaging by following NCCN guidelines and clinical judgment, 6) limiting dose dense chemotherapy to appropriate patients (ER- high risk node negative or node positive), and 7) No Nernyx. Using a cost-effectiveness analysis methodology, we are reviewing costs, effectiveness of interventions, and risks with outcomes measured from side effects, complications, recurrence, and mortality. The improvement in temporal parameters and economic endpoints are being currently monitored retrospectively and prospectively and will be presented.
Citation Format: Annie Tang, Shannon Ugarte, Rohan John, Amal Khoury, Kevin Knopf. Cost-effective care for newly diagnosed breast cancer patients: Think globally, act locally [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-13-07.
Abstract P6-16-03: Surgical management of DCIS during the UK Sloane audit project
Authors: Kirwan Cliona Clare , Stallard Sheila , Mylvaganam Senthurun , Hilton Bridget , Clements Karen , Cheung Shan , Thompson Alistair 
Published: March 2020

Abstract
Introduction
The Sloane Project is a prospective cohort study, including 50% of United Kingdom screen detected ductal carcinoma in situ (DCIS) (2003-2012). We sought to examine the trends in surgical management over time for screen detected DCIS.
Methods
Trends in type of breast surgery were compared with DCIS radiology, pathology and breast size.
Results
Of 9945 patients with complete data undergoing surgical excision, 2274 (22.9%) underwent mastectomy as their first procedure, of whom 1581 (69.5%) had a simple mastectomy. Among 7877 undergoing attempted breast conserving surgery (BCS), 83 (1%) had therapeutic mammoplasty (TM). The 4:1 attempted BCS:mastectomy ratio remained consistent over time. Of attempted BCS, 882 (11.2%) were ultimately converted to mastectomy (28.9% reconstructed).
Over the decade, preoperative radiological estimation of DCIS remained constant at 26mm, however pathological DCIS size steadily increased from 22.4mm (2003-4) to 25.3 (2011-12). There was no corresponding increase in mastectomy, completion mastectomy or re-excision rates. Mean tumour size excised at BCS was 19.3mm (mean), at TM was 32.4mm and at mastectomy was 39.8mm. The rates of simple mastectomy (vs reconstruction) decreased from 77.7% to 61.2% while there was a small increase in TMs (from 0.2% (2 patients) [2003-4] to 1.7% (15 patients) [2011-12]).
There was a statistically (but small [8%] clinically) significant difference in mean breast volume for BCS compared to mastectomy patients (1068ml vs 988ml respectively, Student’s t-test p&lt;0.0001). Mean breast volume (determined from mammography measurements) increased by 16% over the 9 years (from 1013ml to 1171ml), in parallel with increasing national BMI figures for these age groups.
Conclusion
Breast size and pathological size, but not radiological size of screen detected DCIS increased between 2003 and 2012, but BCS rates remained consistent. Interestingly, breast size had no apparent influence on type of surgery, although the decrease in simple mastectomy suggests breast reconstruction increased over time.
Citation Format: Cliona Clare Kirwan, Sheila Stallard, Senthurun Mylvaganam, Bridget Hilton, Karen Clements, Shan Cheung, Alistair Thompson. Surgical management of DCIS during the UK Sloane audit project [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-16-03.
Abstract P6-16-05: Clinical outcomes achieved with brachytherapy vs whole breast irradiation for ductal carcinoma in situ
Authors: Nguyen Katarina T , Francis David , Chandering Thevaa , Pointer Kelli , Anderson Bethany 
Published: March 2020

Abstract
Purpose: To compare the locoregional control achieved with whole breast irradiation (WBI) and accelerated partial breast irradiation (APBI) in women with ductal carcinoma in situ (DCIS).
Methods: We used an institutional, IRB-approved database to retrospectively identify women with primary DCIS lesions less than 3 cm from 1995 to 2014, who underwent negative-margin breast conserving surgery (BCS) followed by either WBI or APBI. Cox-proportional hazard analysis was performed to estimate risks of in-breast tumor recurrence (IBTR) and regional nodal recurrence (RNR), adjusting for age of patient at diagnosis.
Results: Three-hundred and eighty women were identified. Seventy-nine percent received WBI and 21% underwent APBI. Among women receiving WBI, 15.4% received a sequential lumpectomy cavity boost. APBI was delivered via high-dose-rate (HDR) brachytherapy technique, utilizing either a multi-catheter interstitial or single-entry intracavitary approach. The median follow-up time was 6 years for women who received WBI, and 8.9 years for women who received APBI.
The actuarial 10-year IBTR rate was 9.0% for WBI and 8.75% for APBI (p = 0.94). The actuarial 10-year isolated regional nodal recurrence (RNR) rate was 0% for WBI and 2.5% for APBI. Among women who received WBI, the 10-year IBTR rate was 10.0% without lumpectomy cavity boost and 6.36% with boost (p = 0.40). Increasing age correlated with a lower risk of recurrence, regardless of treatment modality (p = 0.005).
Conclusions: No differences in locoregional control was detected for women with DCIS measuring &lt;3 cm, treated with BCS followed by APBI vs WBI.
Citation Format: Katarina T Nguyen, David Francis, Thevaa Chandering, Kelli Pointer, Bethany Anderson. Clinical outcomes achieved with brachytherapy vs whole breast irradiation for ductal carcinoma in situ [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-16-05.
Abstract PD5-04: Tumor-infiltrating lymphocytes evaluation using machine learning image analysis based on core needle biopsy in HER2-positive breast cancer
Authors: Abe Norie , Matsumoto Hirofumi , Takamatsu Reika , Tamaki Kentaro , Takigami Naoko , Uehara Kanou , Kamada Yoshihiko , Tamaki Nobumitsu , Motonari Tokiwa , Nakada Norihiro , Zaha Hisamitsu , Yoshimi Naoki 
Published: March 2020

Abstract
Purpose: To evaluate tumor-infiltrating lymphocytes (TILs) quantitatively in breast cancer and to verify the utility of machine learning image analysis in TIL assessment. Methods: Stromal TILs in 105 Human epidermal growth factor receptor 2 (HER2)-positive invasive breast cancers, diagnosed from patients treated with neoadjuvant anti-HER2 therapy, were evaluated by image analysis of hematoxylin and eosin-stained slides from core needle biopsies. TIL level was determined as the number of TILs per square millimeter of stromal tissue. Associations of TIL level with clinicopathological parameters, pathological response, and clinical outcomes were assessed. Results: Median TIL level were 1287/mm2 (range, 123 - 8101/mm2). Higher TIL level was associated with higher histological grade (P = 0.02), estrogen receptor (ER) negativity (P = 0.036), and pathological complete response (pCR) (P&lt; 0.0001). According to analysis of the receiver operating characteristic curve, a threshold TIL level of 2420/mm2 stroma best discriminated pCR from non-pCR. In multivariate analysis, high TIL levels (&gt;2420/mm2) were significantly associated with pCR (P&lt; 0.0001). On Kaplan-Meier analysis, prognosis was not associated with high or low TIL levels. However, high TIL levels tended to be associated with better prognosis in the HER2+/ER+ subgroup (P = 0.131), but not in the HER2+/ER- subgroup. Conclusions: A machine learning image analysis algorithm could assess TIL level as the number of TILs per square millimeter, contrary to semiquantitative evaluation. TIL level derived from this method could offer an independent predictor of pCR.
Citation Format: Norie Abe, Hirofumi Matsumoto, Reika Takamatsu, Kentaro Tamaki, Naoko Takigami, Kanou Uehara, Yoshihiko Kamada, Nobumitsu Tamaki, Tokiwa Motonari, Norihiro Nakada, Hisamitsu Zaha, Naoki Yoshimi. Tumor-infiltrating lymphocytes evaluation using machine learning image analysis based on core needle biopsy in HER2-positive breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD5-04.
Abstract PD7-03: Adaptive kinome reprogramming in endocrine therapy resistant metastatic breast cancer
Authors: Dustin Derek , Gu Guowei , Chan Doug , Beyer Amanda , Edwards David , Ellis Matthew , Fuqua Suzanne 
Published: March 2020

Abstract
Background: Approximately half of women with estrogen receptor (ER)-positive breast cancer who undergo adjuvant endocrine therapy (ET) develop disease progression and metastasis. Studies have revealed that up to 40% of metastatic patients develop tumors bearing a mutation in ESR1 which is associated with therapeutic resistance and poor prognosis. Studies have shown that cancers can undergo kinome reprogramming in response to therapy and acquired genetic alterations within the tumor. We hypothesize that expression of ESR1 mutations induces kinome reprogramming, which presents novel potential therapeutic targets to selectively treat ESR1 mutant metastatic breast cancer.
Methods: We performed Kinobeads Precipitation (KiP) using broad specificity kinase inhibitors to capture and quantify by MS the level of active kinases in MCF-7 ESR1 wild-type and ESR1 Y537S mutant cells. We performed targeted siRNA screens and immunoblots to validate the hyperactivity of several of these kinases. Specific kinase inhibitors are being used to test their effects on proliferation and invasion in vitro, and in ex vivo organoid growth assays. Xenograft models are being used to evaluate the effects of the inhibitors on primary tumor growth and distant metastasis.
Results: KiP analysis revealed hyperactivation of growth factor receptors, the PI3K/Akt/mTOR pathway, and MAPK pathway, in Y537S mutant cells. We tested specific inhibitors of these pathways, and have shown that the mutant cells have reduced proliferation when these pathways are targeted. We developed organoid growth assays using primary and metastatic tumors from xenograft and PDX models and found that ET in combination with these selected targeted kinase inhibitors decreased the growth of organoids. We are currently testing inhibitors in combination with ET in vivo, and preliminary results demonstrate a significant inhibition of primary tumor growth and distant metastasis. These results suggest that selective inhibition of hyperactivated “reprogrammed” kinase pathways can restore ET sensitivity in ESR1m tumors, and may show promise for use in ER-positive metastatic breast cancer patients.
Citation Format: Derek Dustin, Guowei Gu, Doug Chan, Amanda Beyer, David Edwards, Matthew Ellis, Suzanne Fuqua. Adaptive kinome reprogramming in endocrine therapy resistant metastatic breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD7-03.
Abstract PL2: The role of radiotherapy combined with immunotherapy in oligometastatic cancer
Authors: Weichselbaum RR , Hellman S 
Published: March 2020

Abstract
In 1995 Samuel Hellman and I advanced the hypothesis that many cancers represent a spectrum of disease from purely localized to widespread, highlighting a disease state we termed “oligometastasis.” We proposed that oligometastasis represented an intermediary state between localized and widespread disease that was amenable to cure by metastasis-directed therapies. We also hypothesized that tumor clones that escape systemic therapies, now termed “oligoprogressors,” might be targets for ablation by focal treatments. I will present data supporting the basis and classification of (oligo)metastatic disease, as well as clinical trial results from patients, including those with breast cancer, that informs us regarding future clinical strategies. A decade ago our group noted that large radiation doses used in stereotactic radiotherapy employed in clinical trials of oligometastatic tumors induced immunogenic cell death, which has led us to investigations into the potential interaction between radiotherapy and immunotherapy. I will also present basic and clinical data from investigations into combined radio-immunotherapy treatment and suggest how these investigations might improve treatment of patients.
Citation Format: RR Weichselbaum, S Hellman. The role of radiotherapy combined with immunotherapy in oligometastatic cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PL2.