Pub Date : 2021-02-15DOI: 10.1158/1538-7445.SABCS20-GS3-07
R. Jagsi, K. Griffith, F. Vicini, T. Boike, M. Dominello, G. Gustafson, J. Hayman, J. Moran, J. Radawski, E. Walker, L. Pierce
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
背景:评估医生(MDs)是否准确地检测到患者(pts)的症状是很重要的，因为对症状的识别有助于支持性护理，而且临床试验通常依赖于使用不良事件共同毒性标准(CTCAE)的MD评估。方法:29例乳房肿瘤切除术后接受放疗(RT)的乳腺癌患者被纳入质量倡议MROQC。在2012年1月1日至2020年3月31日期间完成RT的13,725名患者中，9,941名患者在RT期间完成了至少一份pt报告结果(PRO)问卷。在PRO评估后3天内进行MD CTCAE评估时，比较4种症状的pt和MD评分。患者通过一份经批准修改的简短疼痛清单报告乳房疼痛，要求对过去24小时内的疼痛进行评分，分为最严重、最轻微、平均和“现在”。当患者报告中度疼痛(评分4-6)，但MDs在CTCAE上将疼痛分级为0(缺席)，或当患者报告严重疼痛(评分7-10)，但MDs的CTCAE评分≤1时，MDs被认为低估了疼痛。瘙痒和水肿引起的疼痛用改良的皮肤指数测量。如果MDs将瘙痒和水肿分级为不存在(0级)，当患者分别报告经常或一直瘙痒或肿胀时，则认为他们未充分识别瘙痒和水肿。当患者报告大部分时间或总是有明显的疲劳时，如果医学博士将疲劳分级为不存在(0级)，则认为他们未充分认识疲劳。我们描述了在治疗过程中至少一次对这四种症状中的至少一种缺乏认识的患者的比例，并使用多变量逻辑回归来评估这种缺乏认识的预测因子，假设它在少数民族中更常见。结果:3,434/9,940(34.5%)患者报告严重的乳房疼痛，3,039/9,923(30.6%)患者报告瘙痒引起的频繁疼痛，2,363/9,906(23.9%)患者报告水肿引起的频繁疼痛，2,209/8,860(24.9%)患者报告严重疲劳。我们可以评估9868名患者的认知不足，其中37593名患者对pt和MD报告进行了独立的配对观察(35797名在同一天，1796名在3天内)。2094 / 6781例(30.9%)患者报告的中度/重度疼痛，748/ 2039例(36.7%)患者报告的频繁瘙痒，2309 / 4492例(51.4%)患者报告的频繁水肿，390/ 2079例(18.8%)患者报告的严重疲劳存在认知不足。2933 / 5510(53.2%)的患者在治疗过程中至少出现过一次上述四种症状中的至少一种。与识别不足相关的独立因素是(表):年龄更小(OR=1.4和1.2)结论:PRO收集对于试验至关重要，因为依赖CTCAE检测不良事件可能会遗漏重要症状。此外，由于MDs系统地遗漏了某些患者的实质性症状，包括年轻或黑人或其他种族的患者，因此改善症状检测可能是减少RT经验和结果差异的有针对性的机制。引用格式:Reshma Jagsi, Kent A. Griffith, Frank Vicini, Thomas Boike, Michael Dominello, Gregory Gustafson, James A. Hayman, Jean M. Moran, Jeffrey Radawski, Eleanor Walker, Lori J. Pierce，代表密歇根放射肿瘤学质量联盟MROQC。识别在乳房放疗期间症状未被充分认识的患者:多中心队列中患者和医生毒性报告的比较[摘要]。参见:2020年圣安东尼奥乳腺癌虚拟研讨会论文集;2020年12月8-11日;费城(PA): AACR;癌症杂志，2021;81(4增刊):摘要nr GS3-07。
{"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}
Pub Date : 2021-02-15DOI: 10.1158/1538-7445.sabcs20-gs4-02
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
{"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}
Pub Date : 2019-02-15DOI: 10.1158/1538-7445.SABCS18-GS4-02
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
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.
背景:对于乳腺癌手术后哪些淋巴结区域应该进行放射治疗还不确定。放射剂量学的系统评价表明，在淋巴结放射治疗(RT)的随机试验中，现代试验的放射传递质量优于旧试验。方法:我们对随机试验进行了个体患者数据荟萃分析，评估了不同淋巴结区域(包括腋窝、锁骨上窝(SCF)和内乳链(IMC)) RT的益处和风险。符合条件的研究开始于2009年之前，包括随机化或伪随机化(通过左侧和右侧肿瘤)，其中治疗组之间的唯一区别是淋巴结照射的使用或程度。乳房的手术/放疗在双臂中是相同的。分析采用标准对数秩方法，并按研究、年龄、淋巴结状态和随访年份进行分层。-研究根据淋巴结RT组估计的平均心脏剂量和方案是否可能将≥85%的处方剂量递送到目标淋巴结区域进行分类。结果:13132名妇女在14项淋巴结放疗与非淋巴结放疗的比较中获得了信息。有3260例复发，2545例死于乳腺癌，4147例死亡。从1961-1978年开始的8项试验，中位随访时间为9.2年(四分位间距[IQR] 3.4-17.5)年，估计平均心脏剂量和可能的淋巴结剂量> 8gy, 1989-2003年开始的6项研究，平均随访时间为9.1年[IQR] 7.0-11.0]年，估计可能的淋巴结剂量≥85%，估计的平均心脏剂量结论:在老年(1961-78)研究中，局部淋巴结放疗增加了总体死亡风险，可能是由于肺部和心脏的辐射暴露。在最近(1989-2003)的研究中，淋巴结放疗降低了乳腺癌复发率、乳腺癌死亡率和总体死亡率，但没有增加非乳腺癌死亡率。今天的RT带来的比例效益可能更大。个别妇女的绝对收益将取决于她们的绝对复发和乳腺癌死亡风险。引用格式: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.区域淋巴结放疗在早期乳腺癌中的应用:14项临床试验的EBCTCG meta分析[摘要]。2018年圣安东尼奥乳腺癌研讨会论文集;2018年12月4-8日;费城(PA): AACR;癌症杂志，2019;79(4增刊):摘要nr GS4-02。
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Pub Date : 2019-02-15DOI: 10.1158/1538-7445.sabcs18-gs1-06
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
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.
背景:浸润性小叶性乳腺癌(Invasive lobular breast cancer, ILC)是乳腺癌第二常见的组织学类型，占所有浸润性病例的10-15%，通常表达雌激素受体(estrogen receptor, ER，由ESR1基因编码)。对于ILC中与肿瘤进展和内分泌抵抗相关的基因组改变知之甚少。因此，在这里，我们从分子上表征了一系列独特的匹配的原发性和转移性ILC。患者和方法:我们回顾性地鉴定了来自6家机构的129例转移性er阳性ILC患者。经过中心病理检查和原发肿瘤(P)、转移瘤(e)、转移瘤(M)以及正常组织的可用DNA, 80例患者(279份样本)符合本研究的条件。除6例(7.5%)患者外，其余患者在转移性取样前均接受内分泌治疗。低通全基因组和靶基因筛选(N=20个基因)测序分别检测与ILC转移进展相关的拷贝数畸变(copy number aberrations, CNAs)和突变。采用液滴数字PCR (ddPCR)进一步评估ESR1突变。来自IJB (n=413 ILC Ps)、TCGA (n=172 ILC Ps)和MSKCC-IMPACT (n=116 ILC Ms)的公开数据用于比较和验证检测到的ILC改变的频率。间质瘤浸润淋巴细胞(TILs)由两名经验丰富的病理学家评估。结果:总体匹配的CNA比较显示无复发生存率与P或M专有的CNA数量定义的P/M基因组距离显著正相关(r2= 0.52, P)。在免疫浸润方面，Ps中较高的TILs与诊断年龄较小、肿瘤分级高、非经典和小梁混合组织学显著相关。配对分析显示，P和M患者的TIL水平无显著差异，P或M患者的TIL水平与生存率无关。结论:据我们所知，这是最大的转移性ILC系列，其中匹配的P和M样本被询问，揭示了一些基因组改变，其中一些可能是可靶向的，驱动疾病进展和内分泌抵抗。引用格式: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.通过基因组和免疫特征分析原发性和转移性乳腺癌的进展和内分泌抵抗机制[摘要]。2018年圣安东尼奥乳腺癌研讨会论文集;2018年12月4-8日;费城(PA): AACR;癌症杂志，2019;79(4增刊):摘要nr GS1-06。
{"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}
Pub Date : 2019-02-15DOI: 10.1158/1538-7445.SABCS18-GS3-04
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
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
{"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}
Pub Date : 2019-02-15DOI: 10.1158/1538-7445.SABCS18-GS5-02
I. Thune, Anders Husøy, Hanne Frydenberg, V. Flote, F. Fjeldheim, G. F. Bertheussen, S. Lundgren, J. Lømo, E. Wist, A. McTiernan, E. Schlichting
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.
{"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}
Pub Date : 2019-02-15DOI: 10.1158/1538-7445.SABCS18-GS6-04
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
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.
背景:接受辅助治疗的老年BC患者化疗毒性风险增加;然而，没有bc特有的工具来量化这种风险。癌症和衰老研究小组(CARG)开发/验证了针对所有阶段实体瘤的老年患者的化疗毒性评分。本研究的目的是:1)通过开发/验证CARG-BC(老年患者的BC特异性辅助化疗毒性评分)来建立CARG评分，2)评估其与剂量调整、降低相对剂量强度(RDI)和住院治疗的关系。方法:来自16个部位的501例年龄≥65岁的I-III期BC患者(300例发展;2011年验证队列)。化疗前评估包括:CARG化疗毒性评分、BC肿瘤/tx变量和额外的老年评估(GA)项目。NCI CTCAE v 4.0捕获3-5级化学毒物。结果:在501名患者中，28名患者接受了非标准方案，并被排除在外，剩下473名可评估患者:283名发展和190名验证队列。发展组(中位年龄70岁;范围65-85)有I期(39%)，II期(41%)和III期(20%)BC, 65%激素阳性，24%三阴性，27% Her2阳性;37%的人接受了蒽环类药物。3-5级毒性发生率为46%(36%为3级，10%为4级，0.4%为5级)。CARG评分与3-5级毒性显著相关(p)。结论:我们开发并验证了一种风险评分(CARG-BC)，该评分可识别老年pt9s发生辅助BC化疗毒性的风险，并与剂量减少、延迟、RDI降低和住院有关。该工具可被视为辅助tx决策的一部分。引文格式: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。接受辅助/新辅助治疗(佐剂Tx)的老年乳腺癌患者化疗毒性(Chemo Tox)风险评分的开发和验证:一项R01和BCRF资助的前瞻性多中心研究[摘要]。2018年圣安东尼奥乳腺癌研讨会论文集;2018年12月4-8日;费城(PA): AACR;癌症杂志，2019;79(4增刊):摘要nr GS6-04。
{"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}
Pub Date : 2019-02-15DOI: 10.1158/1538-7445.SABCS18-GS1-08
F. André, T. Filleron, C. Ng, F. Bertucci, C. Letourneau, A. Jacquet, S. Piscuoglio, M. Jimenez, T. Bachelot
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.
基本原理:虽然已经做了大量的努力来描述早期乳腺癌的特征，但对转移性乳腺癌的基因组图谱知之甚少。在本研究中，我们对800例转移性乳腺癌进行了全外显子组测序，以确定新的候选靶点，并更好地对符合创新治疗条件的患者进行分层。患者和方法:在精准医学试验(SAFIR01, SAFIR02, PERMED, MOSCATO, SHIVA)的背景下，选择出现转移性乳腺癌并接受活检的患者。使用Hiseq和Novaseq对大于30%的癌细胞和正常DNA进行测序。使用MutSigCV识别驱动程序。基于OncoKB确定体细胞遗传改变的可操作性。利用解构函数对突变特征进行分解。采用cox模型评估预后价值。使用TCGA数据库作为比较器来鉴定转移性样本中富集的基因改变。结果:当前摘要中给出的结果是基于前629例患者的分析。对387例HR+/Her2-乳腺癌患者、186例三阴性乳腺癌患者和32例Her2过表达乳腺癌患者进行了测序。只有9例患者接受了CDK4抑制剂的预处理。24个驱动基因显著突变。在HR+/Her2-乳腺癌患者中，与早期乳腺癌相比，有11个基因在转移性乳腺癌中更频繁地发生突变。这包括TP53(29%)、KMT2C(13%)、NCOR1(8%)、NF1(7%)、RB1(4%)、C16orf3(2%)、FRG1(6%)、ESR1(21%)、RIC8A(4%)、AKT1(7%)、PLSCR5(2%)。此外，在整个人群中，KRAS在3%的样本(G12A/C/R/V)中发现突变，而其在早期乳腺癌中的突变频率为1%。我们进一步评估了突变特征，以便更好地了解哪些突变过程可以驱动癌症进展。与早期HR+/Her2- BC相比，转移性HR+/Her2- mBC表现出APOBEC、S3 (HRD)、S10 (pole相关特征)、S17特征的增加。结论:本研究基于629例患者，确定了HR+/Her2-转移性乳腺癌中富集的11个驱动基因改变和4个突变过程。800名患者的最终结果将被公布。引用格式:Andre F, Filleron T, Ng C, Bertucci F, Letourneau C, Jacquet A, Piscuoglio S, Jimenez M, Bachelot T.转移性乳腺癌的基因组特征[摘要]。2018年圣安东尼奥乳腺癌研讨会论文集;2018年12月4-8日;费城(PA): AACR;癌症杂志，2019;79(4增刊):GS1-08。
{"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}
Pub Date : 2019-02-15DOI: 10.1158/1538-7445.SABCS18-GS1-07
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
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
背景:原发性乳腺癌(BC)的深度测序已经确定了一种异质性的疾病驱动因素，克隆进化和潜在突变过程的证据。随着癌症随着时间的推移和治疗压力的发展，转移性BC (MBC)组织的全基因组测序(WGS)对于进一步了解其基因组成和驱动因素至关重要，从而改善患者管理。方法:根据个性化癌症治疗中心(CPCT-02)的活检方案，前瞻性招募转移组织和匹配的MBC患者(N=501)种系DNA;NCT01855477)，经WGS分析。序列reads被映射到参考基因组，称为体细胞单核苷酸变异(SNV)，小插入和缺失(InDels)和拷贝数变异，突变特征和肿瘤突变负担(TMB);SNV和InDels相对于基因组的数量)。我们的队列中所谓畸变的发生率与先前报道的560例原发性BC的WGS数据(BASIS队列，Nik-Zainal等)进行了比较。结果:根据常规诊断，303例患者(60.5%)为ER+/HER2-， 70例(14%)为三阴性(TNBC)， 95例(19%)为HER2+，其余33例(6.6%)为未知亚型。复发影响基因前5位依次为TP53(47%)、ATM(33%)、MAP2K4(32%)、NCOR1(31%)、ERBB2(30%)。在转移性病变中，中位TMB为2.9 /百万碱基对(IQR: 1.7-5.3)。有趣的是，53例(11%)患者TMB高(≥10)。与原发性BC (BASIS队列)相比，我们发现(亚型特异性)多个基因的改变丰富，如ATM(0.4%至33%)，GPS2(1.3%至29%)，MAP2K4(6.4%至32%)，CBFB(2.7%至25%)，以及先前报道的ESR1(1.3%至20%)。APOBEC特征突变似乎在MBC中富集，而HRD特征突变似乎不那么普遍。正在进行分析，以揭示额外的基因组特征，以及基因组改变与先前治疗和活检后直接接受治疗(即单独内分泌治疗或联合CDK4/6抑制剂和化疗)的独特收集信息的关联。此外，为了排除方法学偏差，BASIS队列的原始数据将通过我们的管道进行处理。结论:这一独特的MBC患者队列的WGS显示出与原发性BC大致相似的基因组成，但在转移性疾病中确实显示出选定驱动突变的亚型特异性富集。本研究提供了更好地了解MBC的肿瘤生物学，可能改善这些患者的管理。引用格式: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。501例转移性乳腺癌患者的基因组图谱[摘要]。2018年圣安东尼奥乳腺癌研讨会论文集;2018年12月4-8日;费城(PA): AACR;癌症杂志，2019;79(4增刊):GS1-07。
{"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}
Pub Date : 2019-02-15DOI: 10.1158/1538-7445.SABCS18-GS3-06
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
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
背景:最近的研究表明，早期ER阳性(ER+)和HER2阴性(HER2-)乳腺癌的女性在诊断后20年内具有持续的复发和癌症相关死亡风险，这突出了ER+乳腺癌的慢性性质，迫切需要确定比标准临床协变量更能预测复发风险的肿瘤特征。然而，由于缺乏长期临床随访和分子信息的大型队列，描述乳腺癌复发动态和晚期复发生物标志物的进展受到阻碍。方法:我们报告了来自英国和加拿大的3240例乳腺癌患者的队列研究结果，随访20年(中位9.75年)，其中1980例伴有原发乳腺肿瘤的分子数据。收集每位患者的局部区域复发(LR)、远处复发(DR)和转移部位的信息。我们开发了一个非同质马尔可夫链模型，该模型考虑了不同的临床终点和时间尺度，以及不同分子亚群特征的死亡率竞争风险和不同的基线危险。该方法能够对临床亚组、PAM50亚组和综合集群中乳腺癌复发的时空动态进行稳健分析，同时也能够预测个体复发风险。结果:我们使用我们的多状态模型来计算经历LR或DR的概率，以及每个临床/分子亚组中平均个体在不同时间间隔从手术，LR或DR的基线过渡概率。这些分析揭示了四种晚期复发ER+(主要是HER2-)亚组，共占所有ER+肿瘤的26%，在诊断后20年内的复发风险很高(中位42-55%)。这四个亚群中的每一个都映射到一个基于基因组拷贝数改变和基因表达定义的整合集群，并丰富了一个特征拷贝数扩增事件:11q13 (CCND1, RSF1)， 8p12 (FGFR1, ZNF703)， 17q23 (RPS6KB1)和8q24 (MYC)。这四个分子亚群在预测晚期DR方面优于标准临床变量。结论:详细了解乳腺癌的转移率和途径及其在不同分子亚型中的变异性，对于设计个性化的乳腺癌治疗方法至关重要。我们描述了一个具有长期临床随访和统计建模框架的分子特征的乳腺癌队列，能够以前所未有的分辨率描绘乳腺癌复发的动态。这些分析揭示了四个晚期复发的ER+亚组和伴随的生物标志物，它们共同定义了复发风险最高的ER+病例的四分之一。我们的研究结果强调了改善患者分层和生物标志物驱动的临床试验针对持续复发风险的乳腺癌患者亚群的机会。引用格式:Curtis C, Rueda OM, Sammut S- j, Chin S- f, Caswell-Jin JL, Seoane JA, Callari M, Batra R, Pereira B, Bruna, Ali HR, Provenzano E, Liu B, Parisien M, Gillett C, McKinney S, Green A, Murphy L, Purushotham A, Ellis I, Pharoah P, Rueda C, Aparicio S, Caldas C.乳腺癌复发动态的分子定义晚期复发er阳性亚群:来自METABRIC研究的结果[摘要]。2018年圣安东尼奥乳腺癌研讨会论文集;2018年12月4-8日;费城(PA): AACR;癌症杂志，2019;79(4增刊):摘要nr GS3-06。
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