General Session Abstracts最新文献

{"title":"Abstract GS3-07: Identifying patients whose symptoms are under-recognized during breast radiotherapy: Comparison of patient and physician reports of toxicity in a multicenter cohort","authors":"R. Jagsi, K. Griffith, F. Vicini, T. Boike, M. Dominello, G. Gustafson, J. Hayman, J. Moran, J. Radawski, E. Walker, L. Pierce","doi":"10.1158/1538-7445.SABCS20-GS3-07","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS20-GS3-07","url":null,"abstract":"BACKGROUND: Evaluating whether physicians (MDs) accurately detect symptoms in patients (pts) is important because recognition of symptoms facilitates supportive care and because clinical trials often rely on MD assessments using the Common Toxicity Criteria for Adverse Events (CTCAE). METHODS: Breast cancer pts who received radiotherapy (RT) after lumpectomy at 29 practices were enrolled in a quality initiative, MROQC. Of 13,725 pts who completed RT between 1/1/2012 and 3/31/2020, 9,941 completed at least one pt-reported outcomes (PRO) questionnaire during RT. Where MD CTCAE assessments were available within 3 days of PRO evaluation, pt and MD ratings of 4 symptoms were compared. Pts reported breast pain via an approved modification of the Brief Pain Inventory, asking for ratings in the last 24 hours of pain at its worst, least, average, and “right now.” MDs were deemed to under-recognize pain when pts reported moderate pain (score 4-6) but MDs graded pain as 0 (absent) on the CTCAE, or when pts reported severe pain (score 7-10) but MDs’ CTCAE grade was ≤1. Bother from pruritis and edema were measured by modified scaled measures adapted from the Skindex. MDs were deemed to under-recognize pruritus and edema if they graded these as absent (grade 0) when pts reported bother often or all of the time from itching or swelling, respectively. MDs were deemed to under-recognize fatigue if they graded fatigue as absent (grade 0) when pts reported having significant fatigue most of the time or always.We describe the proportion of pts for whom under-recognition of at least 1 of these 4 symptoms occurred at least once during the treatment course and use multivariable logistic regression to evaluate predictors of this under-recognition, hypothesizing that it would be more common in racial minorities. RESULTS: 3,434/9,940 pts (34.5%) reported substantial breast pain, 3,039/9,923 (30.6%) frequent bother from pruritus, 2,363/9,906 (23.9%) frequent bother from edema, and 2,209/8,860 (24.9%) severe fatigue. We could evaluate under-recognition in 9,868 pts, with 37,593 independent paired observations of pt and MD reports (35,797 on the same date and 1,796 within 3 days). Under-recognition existed in 2,094/6,781 (30.9%) observations of pt-reported moderate/severe pain, 748/2,039 (36.7%) of pt-reported frequent pruritis, 2,309/4,492 (51.4%) of pt-reported frequent edema, and 390/2,079 (18.8%) of pt-reported severe fatigue. Under-recognition of at least 1 of these 4 symptoms occurred at least once during the pt’s treatment course for 2,933/5,510 (53.2%) of the pts who reported at least 1 substantial symptom during RT.Factors independently associated with under-recognition were (Table): younger age (OR=1.4 and 1.2 for CONCLUSIONS: PRO collection appears essential for trials because relying on the CTCAE to detect adverse events may miss important symptoms. Moreover, since MDs systematically miss substantial symptoms in certain patients, including pts who are younger or ","PeriodicalId":12697,"journal":{"name":"General Session Abstracts","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80614451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract GS4-02: E2112: Randomized phase 3 trial of endocrine therapy plus entinostat/placebo in patients with hormone receptor-positive advanced breast cancer. A trial of the ECOG-ACRIN cancer research group","authors":"R. Connolly, Fengmin Zhao, K. Miller, Min-Jung Lee, R. Piekarz, K. Smith, U. Brown-Glaberman, J. Winn, B. Faller, A. Onitilo, M. Burkard, G. Budd, E. Levine, M. Royce, P. Kaufman, Alexandra Thomas, J. Trepel, A. Wolff, J. Sparano","doi":"10.1158/1538-7445.sabcs20-gs4-02","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs20-gs4-02","url":null,"abstract":"","PeriodicalId":12697,"journal":{"name":"General Session Abstracts","volume":"67 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73294618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract GS4-02: Regional lymph node irradiation in early stage breast cancer: An EBCTCG meta-analysis of 13,000 women in 14 trials","authors":"D. Dodwell, C. Taylor, P. Mcgale, C. Coles, F. Duane, R. Gray, T. Kühn, C. Hennequin, S. Oliveros, Y. Wang, J. Overgaard, P. Poortmans, T. Whelan","doi":"10.1158/1538-7445.SABCS18-GS4-02","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-GS4-02","url":null,"abstract":"Background There is uncertainty as to which lymph node regions should be irradiated following breast cancer surgery. Systematic review of radiation dosimetry indicates that in randomised trials of nodal radiation therapy (RT) versus not, radiation delivery was qualitatively better in modern trials compared to older trials. Methods We undertook an individual patient data meta–analysis of randomised trials assessing the benefits and risks of RT to different lymph node regions including the axilla, supraclavicular fossa (SCF) and internal mammary chain (IMC). Eligible studies started before 2009, and included a randomisation, or pseudo–randomisation (by left–versus–right sided tumours), in which the only difference between treatment groups was the use, or extent, of nodal irradiation. Surgery/RT to the breast was the same in both arms. Analyses used standard log–rank methods, and were stratified by study, age, nodal status and year of follow–up. – Studies were categorised according to estimated mean heart dose in the nodal RT arm and whether regimens were likely to have delivered ≥85% of prescribed dose to target nodal regions. Results Information was available on 13,132 women in 14 comparisons of nodal RT versus not. There were 3260 recurrences, 2545 deaths from breast cancer and 4147 deaths overall. Eight trials starting 1961–1978, with median follow–up 9.2 (interquartile [IQR] range 3.4–17.5) years, had estimated >8 Gy mean heart dose and likely nodal dose Six studies starting 1989–2003, with a mean follow–up 9.1 [IQR 7.0–11.0] years, had likely nodal dose ≥85%, and estimated mean heart dose Conclusions RT to regional lymph nodes in older (1961–78) studies increased the overall risk of death, probably explained by radiation exposure of the lungs and heart. Nodal RT in more recent (1989–2003) studies reduced breast cancer recurrence, breast cancer mortality and overall mortality without increasing non–breast cancer mortality. The proportional benefits from today9s RT may be larger. Absolute benefits for individual women will depend on their absolute recurrence and breast cancer mortality risks. Citation Format: Dodwell D, Taylor C, McGale P, Coles C, Duane F, Gray R, Kuhn T, Hennequin C, Oliveros S, Wang Y, Overgaard J, Poortmans P, Whelan T. Regional lymph node irradiation in early stage breast cancer: An EBCTCG meta-analysis of 13,000 women in 14 trials [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS4-02.","PeriodicalId":12697,"journal":{"name":"General Session Abstracts","volume":"46 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73776775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract GS1-06: Unraveling lobular breast cancer progression and endocrine resistance mechanisms through genomic and immune characterization of matched primary and metastatic samples","authors":"C. Desmedt, F. Richard, S. Majjaj, Julien Pingitore, David N. Brown, F. Rothé, C. Marchiò, F. Clatot, O. Mariani, B. Boeckx, G. Rouas, F. Bertucci, C. Galant, G. V. D. Eynden, R. Salgado, D. Lambrechts, A. Vincent-Salomon, M. Piccart, G. Pruneri, D. Larsimont, C. Sotiriou","doi":"10.1158/1538-7445.sabcs18-gs1-06","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs18-gs1-06","url":null,"abstract":"Background: Invasive lobular breast cancer (ILC) represents the second most common histology of breast cancer, accounts for 10-15% of all invasive cases and generally expresses the estrogen receptor (ER, coded by the ESR1 gene). Little is known about the genomic alterations associated with tumor progression and endocrine resistance in ILC. Here, we therefore molecularly characterized a unique series of matched primary and metastatic ILC. Patients and methods: We retrospectively identified 129 metastatic ER-positive ILC patients from 6 institutions. Following central pathology review and available DNA from the primary tumor (P), the metastasi(e)s (M), as well as from normal tissue, 80 patients (279 samples) were eligible for this study. All but 6 patients (7.5%) received endocrine treatment before metastatic sampling. Low pass whole genome and targeted gene screen (N=20 genes) sequencing was conducted to detect copy number aberrations (CNAs) and mutations associated with ILC metastatic progression respectively. ESR1 mutations were further assessed using droplet digital PCR (ddPCR). Publicly available data from IJB (n=413 ILC Ps), TCGA (n=172 ILC Ps), and MSKCC-IMPACT (n=116 ILC Ms) were used to compare and validate the frequencies of the detected alterations in ILC. Stromal tumor infiltrating lymphocytes (TILs) were assessed by two experienced pathologists. Results: The overall matched CNA comparison revealed a significant positive association between relapse-free survival and the P/M genomic distance defined by the number of CNAs private to P or M (r2= 0.52, p Regarding the immune infiltration, higher TILs in Ps were significantly associated with younger age at diagnosis, high grade tumors, and with mixed non-classic and trabecular histology. A paired analysis revealed no significant difference in TIL levels between P and M. TIL levels in the P or M were not associated with survival. Conclusion: This is to our knowledge the largest metastatic ILC series in which matched P and M samples were interrogated, revealing several genomic alterations, some of which potentially targetable, driving disease progression and endocrine resistance. Citation Format: Desmedt C, Richard F, Majjaj S, Pingitore J, Brown D, Rothe F, Marchio C, Clatot F, Mariani O, Boeckx B, Rouas G, Bertucci F, Galant C, Van den Eynden G, Salgado R, Lambrechts D, Vincent-Salomon A, Piccart M, Pruneri G, Larsimont D, Sotiriou C. Unraveling lobular breast cancer progression and endocrine resistance mechanisms through genomic and immune characterization of matched primary and metastatic samples [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS1-06.","PeriodicalId":12697,"journal":{"name":"General Session Abstracts","volume":"273 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76571289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract GS3-04: A prospective randomized multi-center open-label phase III trial of extending aromatase-inhibitor adjuvant therapy to 10 years - Results from 1697 postmenopausal women in the N-SAS BC 05 trial: Arimidex extended adjuvant randomized study (AERAS)","authors":"S. Ohtani, K. Iijima, K. Higaki, Y. Sato, Y. Hozumi, Y. Hasegawa, H. Takei, M. Tanaka, H. Yagata, H. Masuoka, M. Tanabe, C. Egawa, Y. Komoike, S. Saji, Takashi Nakamura, Y. Yanagita, H. Ohtsu, H. Mukai, T. Iwase","doi":"10.1158/1538-7445.SABCS18-GS3-04","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-GS3-04","url":null,"abstract":"Background: Treatment with an aromatase inhibitor for 5 years as up-front monotherapy or after tamoxifen therapy for 2-3 years is the treatment of choice for hormone-receptor-positive breast cancer in postmenopausal women. Extending treatment with an aromatase inhibitor to 10 years may reduce the risk of breast cancer recurrence. Methods: We conducted a prospective randomized multi-center open-label phase III trial to assess the effect of the extended use of anastrozole for an additional 5 years. Postmenopausal patients with stageI-III, hormone-receptor-positive breast cancer, disease-free after 5 years of either anastrozole alone or tamoxifen 2-3 years followed by anastrozole 3-2 years were randomized to continual group with anastrozole for an additional 5 years or stop group without an additional anastrozole. Our primary end point was disease-free survival. Results: We enrolled 1697 women. After a median follow up of 4.9 years, there were 149 events involving disease recurrence or the occurrence of contralateral breast cancer (51 in continual group and 98 in stop group) and 7 deaths (3 in continual group and 4 in stop group). The 5-year disease-free survival rate was 91.9% (95% confidence interval [CI], 89.4 to 93.8) in continual group and 84.4% (95% CI: 80.0 to 88.0) in stop group (hazard ratio for disease-free survival,0.548 ;P=0.0004. by a two-sided log-rank test stratified according to nodal status, prior adjuvant chemotherapy, institution, and choice of anastrozole or tamoxifen). The rate of 5-year overall survival was 99.5% in continual group and 99.6% in stop group. (hazard ratio,1.389 ;P=0.665). The rate of 5-year distant disease-free survival was 97.2% in continual group and 94.3% in stop group (hazard ratio,0.514 ;P=0.0077). Bone-related adverse events were observed more frequently among patients in continual group than among patients in stop group, including a higher incidence of bone pain, stiff joints, bone fractures, and new-onset osteoporosis. Conclusion: The extension of treatment with an adjuvant aromatase inhibitor (anastrozole) to 10 years resulted in significantly higher rates of disease-free survival and distant disease-free survival than those with no additional anastrozole, but the rate of overall survival was not different between two groups. Our study shows that it is safe and beneficial for postmenopausal patients with hormone-receptor-positive breast cancer to take an anastrozole as adjuvant therapy for an additional 5 years after initial treatment. (UMIN:000000818) Citation Format: Ohtani S, Iijima K, Higaki K, Sato Y, Hozumi Y, Hasegawa Y, Takei H, Tanaka M, Yagata H, Masuoka H, Tanabe M, Egawa C, Komoike Y, Saji S, Nakamura T, Yanagita Y, Ohtsu H, Mukai H, Iwase T. A prospective randomized multi-center open-label phase III trial of extending aromatase-inhibitor adjuvant therapy to 10 years - Results from 1697 postmenopausal women in the N-SAS BC 05 trial: Arimidex extended adjuvant randomized study (AERAS) [abstrac","PeriodicalId":12697,"journal":{"name":"General Session Abstracts","volume":"134 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85615312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract GS5-02: Cardiovascular function and the effect of exercise training during adjuvant breast cancer treatment. Results from The EBBA-II trial","authors":"I. Thune, Anders Husøy, Hanne Frydenberg, V. Flote, F. Fjeldheim, G. F. Bertheussen, S. Lundgren, J. Lømo, E. Wist, A. McTiernan, E. Schlichting","doi":"10.1158/1538-7445.SABCS18-GS5-02","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-GS5-02","url":null,"abstract":"Background: Breast cancer survival rates have improved, but cardiovascular disease is a competing cause of death among breast cancer survivors, and treatment-induced cardio-toxicity remains a major concern. The effect of aerobic exercise on cardiovascular function during adjuvant breast cancer treatment is not yet well established. Material & methods: The women participating in the Energy Balance and Breast Cancer Aspect (EBBA)-II trial are aged 18-75 years and diagnosed with stage I-II breast cancer. VO2max was assessed at three separate times, prior to surgery and at 6 and 12 months after, using a maximum exercise test on a treadmill (modified Balke protocol).The patients were randomized after surgery to a control group (n=188, usual care) or an intervention group (n=187) stratified by menopausal status. The 12 months exercise intervention program started 2-3 weeks after surgery and the patients received a detailed training program based on their own VO2max at baseline. They met for training sessions in groups of 10-12 women for 60 minutes twice a week during a 12 month period, and were in addition asked to perform at least 120 minutes of exercise at home (a total of 240 minutes of exercise weekly).Analyses were done on an intention-to-treat basis (NCT02240836). Preliminary results: Breast cancer patients (n=375) with a mean age at diagnosis of 55.2 years (27.0-75.0 years) had a mean body mass index (BMI) of 25.1kg/m2, a mean VO2max before surgery of 31.5 ml•min−1•kg−1, and 57 % of the patients underwent chemotherapy (paclitaxel, epirubicin/cyclophosphamide based adjuvant chemotherapy). Comparing the intervention group to the control group, the intervention group had a decrease in VO2max of 2.7% after 6 months, but they improved their VO2max by 2.3 % at 12 months compared to before surgery (p=0.001). Breast cancer patients in the control group had a 10 % reduction in VO2max 6 months after surgery (p Conclusion: Our findings strongly support that tailored exercise training during adjuvant breast cancer treatment may counteract a decline in cardiovascular function, and in particular among those receiving chemotherapy. Our study supports incorporation of supervised clinical exercise programs into breast cancer treatment guidelines. Final results of the trial at SABCS 2018 (the trial closes October 15, 2018) total included N=539 (NCT02240836) Citation Format: Thune I, Husoy A, Frydenberg H, Flote VG, Fjeldheim F, Bertheussen GF, Lundgren S, Lomo J, Wist EA, McTiernan A, Schlichting E. Cardiovascular function and the effect of exercise training during adjuvant breast cancer treatment. Results from The EBBA-II trial [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS5-02.","PeriodicalId":12697,"journal":{"name":"General Session Abstracts","volume":"47 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86503598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract GS6-04: Development and validation of a chemotherapy toxicity (Chemo Tox) risk score for older patients (Pts) with breast cancer (BC) receiving adjuvant/neoadjuvant treatment (Adjuvant Tx): A R01 and BCRF funded prospective multicenter study","authors":"A. Hurria, A. Magnuson, C. Gross, W. Tew, H. Klepin, T. Wildes, H. Muss, E. Dotan, R. Freedman, T. O'Connor, W. Dale, H. Cohen, V. Katheria, Anait Arsenyan, Abrahm Levi, Heeyoung Kim, C-L Sun","doi":"10.1158/1538-7445.SABCS18-GS6-04","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-GS6-04","url":null,"abstract":"Background: Older pts with BC receiving adjuvant tx are at increased risk of chemo tox; however, no BC-specific tool exists to quantify this risk. The Cancer and Aging Research Group (CARG) developed/validated a chemo tox score for older pts with all stages of solid tumor. The goals of this study were to: 1) build upon the CARG score by developing/validating CARG-BC (a BC specific adjuvant chemo tox score for older pts) and 2) evaluate its association with dose modifications, reduced relative dose intensity (RDI) and hospitalizations. Methods: 501 pts age ≥65 with stage I-III BC from 16 sites were accrued (300 development; 201 validation cohort). A pre-chemo assessment captured: CARG chemo tox score, BC tumor/tx variables, and additional geriatric assessment (GA) items. Grade 3-5 chemo tox by NCI CTCAE v 4.0 was captured. Univariate analysis identified chemo tox risk factors (p Results: Among 501 pts, 28 received non-standard regimens and were excluded, leaving 473 evaluable pts: 283 development and 190 validation cohort. The development cohort (median age 70; range 65-85) had Stage I (39%), II (41%), & III (20%) BC with 65% hormone positive, 24% triple negative, 27% Her2 positive; and 37% received an anthracycline. Grade 3-5 tox occurred in 46% (36% grade 3, 10% grade 4, 0.4% grade 5). The CARG score was significantly associated with grade 3-5 tox (p Conclusions: We developed and validated a risk score (CARG-BC) which identifies an older pt9s risk for adjuvant BC chemo tox and is associated with dose reduction, delay, reduced RDI, and hospitalization. This tool could be considered as a part of adjuvant tx decision-making. Citation Format: Hurria A, Magnuson A, Gross CP, Tew WP, Klepin HD, Wildes TM, Muss HB, Dotan E, Freedman R, O9Connor T, Dale W, Cohen HJ, Katheria V, Arsenyan A, Levi A, Kim H, Sun C-L. Development and validation of a chemotherapy toxicity (Chemo Tox) risk score for older patients (Pts) with breast cancer (BC) receiving adjuvant/neoadjuvant treatment (Adjuvant Tx): A R01 and BCRF funded prospective multicenter study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS6-04.","PeriodicalId":12697,"journal":{"name":"General Session Abstracts","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83888569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract GS1-08: Genomic characterisation of metastatic breast cancer","authors":"F. André, T. Filleron, C. Ng, F. Bertucci, C. Letourneau, A. Jacquet, S. Piscuoglio, M. Jimenez, T. Bachelot","doi":"10.1158/1538-7445.SABCS18-GS1-08","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-GS1-08","url":null,"abstract":"Rationale: while large efforts have been done to characterize early breast cancer, little is known about the genomic landscape of metastatic breast cancer. In the present study, we performed whole exome sequencing of 800 metastatic breast cancers, in order to identify new candidate targets and better stratify patients eligible for innovative therapies. Patients and Methods: Patients were selected to present a metastatic breast cancer and to have received a biopsy in the context of precision medicine trials (SAFIR01, SAFIR02, PERMED, MOSCATO, SHIVA). Samples with >30% cancer cells, and normal DNA, were sequenced using Hiseq and Novaseq. Drivers were identified using MutSigCV. Actionability of somatic genetic alterations was determined based on OncoKB. Decomposition of mutational signatures was performed using deconstructSigs. Prognostic value was assessed using a cox model. TCGA database was used as comparator to identify gene alterations enriched in metastatic samples. Results: results presented in the current abstract are based on the first 629 patients analyzed.Sequencing was performed in 387 patients with HR+/Her2- breast cancer, 186 triple negative breast cancers, and 32 Her2-overexpressing breast cancers. only 9 patients received a pretreatment with a CDK4 inhibitor. 24 driver genes were significantly mutated. In patients with HR+/Her2- breast cancer, 11 genes were found more frequently mutated in the metastatic setting as compared to early stage breast cancer. This includes TP53 (29%), KMT2C (13%), NCOR1 (8%), NF1 (7%), RB1 (4%), C16orf3 (2%), FRG1 (6%), ESR1 (21%), RIC8A (4%), AKT1 (7%), PLSCR5 (2%). In addition, in the whole population, KRAS was found mutated in 3% of samples (G12A/C/R/V) while its frequency of mutation in early breast cancer is We further assessed the mutational signatures in order to better understand which mutational processes could drive cancer progression. Metastatic HR+/Her2- mBC presented an increase in APOBEC, S3 (HRD), S10 (POLE-associated signature), S17 signatures as compared to early HR+/Her2- BC. Conclusion: the present study, based on 629 patients, identifies 11 driver gene alterations and four mutational processes enriched in HR+/Her2- metastatic breast cancers. Final results on 800 patients will be presented. Citation Format: Andre F, Filleron T, Ng C, Bertucci F, Letourneau C, Jacquet A, Piscuoglio S, Jimenez M, Bachelot T. Genomic characterisation of metastatic breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS1-08.","PeriodicalId":12697,"journal":{"name":"General Session Abstracts","volume":"2018 48","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91549083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract GS1-07: The genomic landscape of 501 metastatic breast cancer patients","authors":"L. Angus, S. Wilting, J. V. Riet, M. Smid, T. Steenbruggen, V. Tjan-Heijnen, M. Labots, Jmgh van Riel, H. Bloemendal, N. Steeghs, Harmen van de Werken, M. Lolkema, E. Voest, A. Jager, E. Cuppen, S. Sleijfer, J. Martens","doi":"10.1158/1538-7445.SABCS18-GS1-07","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-GS1-07","url":null,"abstract":"Background: In depth sequencing of primary breast cancer (BC) has identified a heterogeneous repertoire of disease drivers, evidence of clonal evolution and underlying mutational processes. As cancer evolves over time and under treatment pressure, whole genome sequencing (WGS) of metastatic BC (MBC) tissue is crucial to gain further insight into its genetic make-up and driving forces, thereby allowing improved patient management. Methods: Metastatic tissue and matched germline DNA of patients with MBC (N=501) were prospectively recruited under the biopsy protocol of the Center of Personalized Cancer Treatment (CPCT-02; NCT01855477) and analyzed by WGS. Sequence reads were mapped to the reference genome to call somatic single nucleotide variants (SNV), small insertions and deletions (InDels) and copy number variations from which mutational signatures and tumor mutational burden (TMB; the number of SNV and InDels relative to the genome) were derived. The incidence of called aberrations in our cohort was compared to previously reported WGS data of 560 primary BC (BASIS cohort, Nik-Zainal et al. Nature 2016) (Table 1). Results: According to routine diagnostics 303 patients (60.5%) were ER+/HER2-, 70 (14%) triple negative (TNBC), 95 (19%) HER2+ and the remaining 33 (6.6%) had as of yet an unknown subtype. Top 5 recurrently affected genes were TP53 (47%), ATM (33%), MAP2K4 (32%), NCOR1 (31%), ERBB2 (30%). In the metastatic lesions, median TMB was 2.9 per million base pairs (IQR: 1.7-5.3). Interestingly, 53 (11%) patients had a high TMB (≥10). Compared to primary BC (BASIS cohort), we found (subtype-specific) enrichment of alterations in multiple genes such as ATM (0.4% to 33%) , GPS2 (1.3% to 29%) , MAP2K4 (6.4% to 32%), CBFB (2.7% to 25%) , and, as previously reported, ESR1 (1.3% to 20%). APOBEC signature mutations appeared to be enriched in MBC while HRD signature mutations seemed less prevalent. Analyses to reveal additional genomic features is ongoing as well as the association of genomic alterations with uniquely collected information on prior treatments and response to treatment received directly after biopsy (i.e. endocrine therapy alone or combined with CDK4/6 inhibitors and chemotherapy). Also, to exclude methodological bias the raw data of the BASIS cohort will be processed through our pipeline. Conclusion: WGS of this unique cohort of patients with MBC shows a genetic make-up roughly similar to primary BC, but does show subtype-specific enrichment of selected driver mutations in metastatic disease. This study provides better insight into the tumor biology of MBC potentially improving management of these patients. Citation Format: Angus L, Wilting SM, van Riet J, Smid M, Steenbruggen TG, Tjan-Heijnen VC, Labots M, van Riel JM, Bloemendal HJ, Steeghs N, van de Werken HJ, Lolkema MP, Voest EE, Jager A, Cuppen E, Sleijfer S, Martens JW. The genomic landscape of 501 metastatic breast cancer patients [abstract]. In: Proceedings of the 2018 San Ant","PeriodicalId":12697,"journal":{"name":"General Session Abstracts","volume":"111 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84307740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract GS3-06: Dynamics of breast cancer relapse reveal molecularly defined late recurring ER-positive subgroups: Results from the METABRIC study","authors":"C. Curtis, O. Rueda, S. Sammut, S. Chin, Jennifer L. Caswell-Jin, J. Seoane, M. Callari, R. Batra, Bernard Pereira, A. Bruna, H. R. Ali, E. Provenzano, B. Liu, M. Parisien, C. Gillett, S. McKinney, A. Green, L. Murphy, A. Purushotham, I. Ellis, P. Pharoah, C. Rueda, S. Aparicio, C. Caldas","doi":"10.1158/1538-7445.SABCS18-GS3-06","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-GS3-06","url":null,"abstract":"Background: Recent studies have demonstrated that women with early stage ER-positive (ER+) and HER2-negative (HER2-) breast cancer have a persistent risk of recurrence and cancer related death up to 20 years post diagnosis, highlighting the chronic nature of ER+ breast cancer and critical need to identify tumor characteristics that are more predictive of risk of recurrence than standard clinical covariates. However, progress in delineating the dynamics of breast cancer relapse and biomarkers of late recurrence has been hindered by the lack of large cohorts with long-term clinical follow-up and molecular information. Methods: We report the results of a cohort of 3,240 breast cancer patients from the United Kingdom and Canada with 20 years of follow-up (median 9.75 years), including 1,980 with accompanying molecular data from the primary breast tumor. Information for each patient on loco-regional recurrence (LR), distant recurrence (DR), and site(s) of metastases was collected. We developed a non-homogenous Markov chain model that accounted for different clinical endpoints and timescales, as well as competing risks of mortality and the distinct baseline hazards that characterize different molecular subgroups. This approach enabled robust analysis of the spatio-temporal dynamics of breast cancer recurrence across the clinical subgroups, PAM50 subgroups and the integrative clusters, while also enabling individual risk of relapse predictions. Results: We employed our multistate model to compute the probability of experiencing a LR or DR, as well as the baseline transition probabilities from surgery, LR or DR at various time intervals for average individuals in each of the clinical/molecular subgroups. These analyses reveal four late-recurring ER+ (predominantly HER2-) subgroups, together accounting for 26% of all ER+ tumors, with high (median 42-55%) risk of recurrence up to 20 years post-diagnosis. Each of these four subgroups maps to one of the Integrative Clusters, defined based on genomic copy number alterations and gene expression, and is enriched for a characteristic copy number amplification events: 11q13 (CCND1, RSF1), 8p12 (FGFR1, ZNF703), 17q23 (RPS6KB1) and 8q24 (MYC). These four molecular subgroups are superior in predicting late DR than standard clinical variables. Conclusions: A detailed understanding of the rates and routes of metastasis and their variability across the distinct molecular subtypes is essential for devising personalized approaches to breast cancer care. We describe a molecularly characterized breast cancer cohort with long-term clinical follow-up and a statistical modeling framework, enabling delineation of the dynamics of breast cancer recurrence at unprecedented resolution. These analyses reveal four late recurring ER+ subgroups and accompanying biomarkers that collectively define the quarter of ER+ cases at highest risk of recurrence. Our findings highlight opportunities for improved patient stratification and biomark","PeriodicalId":12697,"journal":{"name":"General Session Abstracts","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83238176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}