Skip to main content
JCO Precision Oncology logoLink to JCO Precision Oncology
. 2017 Aug 16;1:PO.17.00076. doi: 10.1200/PO.17.00076

Participant Attitudes Toward an Intensive Trial of Multiple Biopsies, Multidimensional Molecular Analysis, and Reporting of Results in Metastatic Triple-Negative Breast Cancer

Nicole M Kuderer 1, Kimberly A Burton 1, Sibel Blau 1, Francis Senecal 1, Vijayakrishna K Gadi 1, Stephanie Parker 1, Elisabeth Mahen 1, David Veenstra 1, Josh J Carlson 1, Gary H Lyman 1, C Anthony Blau 1,
PMCID: PMC7446457  PMID: 32913975

Abstract

Purpose

Multidimensional molecular analysis of tumor tissue intensively over space and time can provide insight into how cancers evolve and escape treatment. Attitudes of participants in such trials have not been assessed. We explored patient views regarding an intensive study incorporating multiple biopsies, multidimensional molecular testing, and drug response predictions that are reported to the oncologist and patient.

Patients and Methods

A structured, self-administered survey was conducted among the first 15 patients enrolled in ITOMIC-001 (Intensive Trial of Omics in Cancer). Patients with metastatic triple-negative breast cancer were accrued at two sites in Washington state. Surveys containing 17 items were administered at enrollment and after the return of results. Surveys explored perceptions regarding risks, personal benefits, benefits to others, uncertainties associated with interpreting complex molecular results, concerns regarding multiple biopsies, and potential loss of confidentiality. At follow-up, three additional unique items explored patient coping.

Results

All participants expressed a strong desire for their experiences to benefit others, and all perceived a higher likelihood of deriving benefit than described during detailed consent discussions. Loss of confidentiality ranked lowest among patient concerns. Despite acknowledging uncertainties and risks inherent in complex molecular testing for clinical reporting, participants wanted access to findings in evaluating treatment choices, even if the best available evidence was weak. Follow-up surveys demonstrated relatively little change in attitudes, although concern about study biopsies generally declined. Study participation helped several patients cope better with their disease.

Conclusion

In advanced breast cancer, these findings demonstrate the feasibility of engaging motivated patients in trials that navigate the uncertainties associated with intensive spatial and longitudinal multidimensional molecular testing for the purpose of advancing precision medicine.

INTRODUCTION

Molecular profiling can provide insight into tumor heterogeneity across space and over time,1-10 uncover patterns associated with treatment response and resistance,11-17 and ultimately, it is hoped, allow patients with cancer to receive drugs that are reliably effective.18-24 Because only a small fraction of the information extractable from a tumor sample can be exploited for therapy, many molecular drug-matching efforts rely on targeted sequencing.25-29 However, targeted sequencing fails to capture molecular features that may eventually prove clinically useful.30-33

The manner and extent to which results from complex molecular testing should be shared with patients remain subject to debate.34-41 Many oncologists are poorly equipped to interpret molecular test results42-46; no guidelines exist to inform these discussions,39,43,45-47 and patient preferences need to be better understood.39,43,47-55

Longitudinal monitoring can provide insight into how cancers evolve and escape treatment.1,2,4,8-10,12-15,17,56,57 However, repeated tumor biopsies are expensive and can cause serious complications.58 One method for circumventing this challenge relies on analyzing circulating cell-free DNA. However, we and others have found significant discordance between the results of next-generation sequencing testing of tumor tissue versus circulating cell-free DNA.59-62

To address these obstacles, we initiated ITOMIC-001 (Intensive Trial of Omics in Cancer; ClinicalTrials.gov identifier: NCT01957514). ITOMIC-001 enrolls patients with metastatic triple-negative breast cancer and involves repeated biopsies of multiple metastatic sites over time, an extensive multidimensional molecular analysis, a distributed network of investigators to analyze results and predict drug susceptibilities,63 and return of results to the patient and her oncologist. At their discretion, the patient can then be treated with the predicted drugs, allowing hypothesized drug susceptibilities to be tested in each patient.

ITOMIC-001 raises important questions regarding the engagement of patients with cancer in an intensive and exploratory research effort. Do patients with cancer understand the risks and uncertainties of receiving treatments on the basis of results from genome-wide analyses? What motivates their participation? How troublesome do patients find the prospect of undergoing multiple biopsies? Our objective was to address these and other questions using surveys administered to patients enrolled in ITOMIC-001.

PATIENTS AND METHODS

ITOMIC-001

Study design.

ITOMIC-001 was launched in October 2013 and has been described previously.63 For the first 15 patients described here, enrollment was restricted to those with metastatic triple-negative breast cancer who were platinum naive and scheduled to receive cisplatin. Research biopsies were performed before cisplatin administration, after discontinuation of cisplatin, and after discontinuation of subsequent therapies. Fifteen patients were enrolled by March 2016, and all surveys were completed by November 2016. ITOMIC-001 involves extensively characterizing the molecular features of a patient’s cancer with biopsies of up to seven metastatic sites (limited to two high-risk sites) in a single setting (metastatic sites were typically sampled between five and 10 times); performing whole-genome sequencing (or whole-exome sequencing), RNA sequencing, and deep sequencing of a panel of cancer-associated genes on multiple samples; employing a distributed network of experts to analyze findings and suggest treatments; reporting results to clinicians and participants for shared decision making; and repeating biopsies before switching to other drug treatments. Outside of the trial, we offer an intensive drug- and clinical trial–matching process to help patients who wish to be treated in accordance with our predictions access the recommended drugs. Patients were contacted 1 day and 1 week after biopsies to assess for adverse events (additional details provided in Data Supplement).

Informed consent.

The study has been approved by the Fred Hutchinson Cancer Research Center Institutional Review Board. The consent process was intended to clearly emphasize that patients are not expected to benefit directly from their participation, in addition to describing potential risks associated with extensive genomic testing (additional details provided in Data Supplement).

Surveys

Participants were asked to complete structured, self-administered surveys that gauged their understanding and attitudes regarding key features of ITOMIC-001. Individual survey items and major thematic domains are listed in Table 1. Surveys were completed at baseline and within 1 month after receipt of the first molecular ITOMIC report describing expert panel findings. Surveys were completed at the patient’s convenience, typically at home, and research staff members were not present.

Table 1.

Survey Items and Corresponding Thematic Domains

graphic file with name PO.17.00076t1.jpg

Statistical Methods

Survey questions were organized using a five-level Likert scale.64 Participants chose from among five responses for each survey item: agree strongly, agree a little, neither agree nor disagree, disagree a little, or disagree strongly. For purposes of analysis, these responses were transformed into five ordinal numeric values ranging from 2 (agree strongly) to −2 (disagree strongly). Descriptive statistical analyses of the numeric baseline and follow-up survey results are based on the mean and standard deviation (SD) calculated for each item across all respondents. Two of the three items unique to the follow-up survey varied response options because of the nature of the items (M19 and M20). These options were a great deal, a good deal, somewhat, a little, or not at all (Table 2).

Table 2.

Participant Responses (n = 10) for Three Survey Items Assessed at Follow-Up (M18-M20) Only

graphic file with name PO.17.00076t2.jpg

RESULTS

Study Population and Survey Items

Survey items and major themes are listed in Table 1. Demographics of the 15 patients are summarized in Table 3 and the Data Supplement. Most participants were postmenopausal, employed, and married. Five of 15 participants did not complete the follow-up survey because of death (n = 3) or study withdrawal (n = 2). One participant required hospitalization for pain control because of skin biopsies that temporarily prevented her from taking the baths needed to alleviate discomfort associated with cutaneous infiltration of inflammatory breast cancer. No other study-related serious adverse events occurred. Among all participants, a total of 141 study-related biopsies were performed (mean per patient, 9.4; range, one to 18 biopsies), involving a total of 33 distinct anatomic sites (mean per patient, 2.2; range, one to five sites; Data Supplement). Ten patients (67%) were able to access a suggested drug or drug combination including approved drugs (n = 3) or off-label drugs (n = 9) through established clinical trials (n = 3) or single-patient investigational new drug applications (n = 3).

Table 3.

Patient Baseline Demographic and Clinical Characteristics (N = 15)

graphic file with name PO.17.00076t3.jpg

Baseline Survey (M1-M17)

Figure 1 depicts responses to the baseline survey items averaged across all 15 patients. Individual responses are shown in the Data Supplement.

Fig 1.

Fig 1.

Fig 1.

Mean response scores for each of the 17 survey items reported at baseline and distributions of individual responses (N = 15). (A-E) At the far left, each survey item is listed. (A1-E1) Left graphs display mean response scores on the x-axis, and whiskers denote standard deviations. The y-axis denotes individual survey items. Survey response scores correspond to: 2 = agree strongly, 1 = agree a little, 0 = neither agree nor disagree, −1 = disagree a little, and −2 = disagree strongly. (A2-E2) Right graphs show the number of patients in each response category; the x-axis reflects the percentage of patients in each category.Dark blue = agree strongly, light blue = agree a little, gold = neither agree nor disagree, gray = disagree a little, and red = disagree strongly.

Recall of information from consent (M1-3).

Three survey items assessed participants’ understanding of the complexities associated with multidimensional molecular testing. Responses were broadly consistent with information provided during consent (Fig 1A; Data Supplement). In response to survey item M1 stating “the results of genetic testing can be extremely difficult to interpret,” eight patients agreed strongly, one agreed a little, and the remaining six neither agreed nor disagreed. In response to M2 stating “difficulties in interpreting the results of genetic testing may lead my doctor to use a treatment that is ineffective,” four patients agreed strongly, five agreed a little, and six neither agreed nor disagreed. In response to M3 stating “difficulties in interpreting the results of genetic testing may lead my doctor to use a treatment that inadvertently causes harm,” three patients agreed strongly, six agreed a little, and six neither agreed nor disagreed. Whereas six patients responded neutrally to each item, only four provided neutral responses across all survey items in this category, and no patient disagreed with any of the items in this category. These results suggest that most patients understand the difficulties associated with interpreting results from high-dimensional molecular testing.

Perceptions of risk (M4-7).

Four survey items assessed concerns regarding risks associated with study participation (Fig 1B; Data Supplement). There was wide variation in responses to M4 stating “I find the large number of biopsies that are required as part of this protocol to be distressing.” One patient agreed strongly, five agreed a little, four disagreed strongly, and the remaining five neither agreed nor disagreed. In response to M5 stating “I am worried about the potential loss of confidential information that may result from my participation in this study,” one patient agreed strongly, one agreed a little, two disagreed a little, and 11 disagreed strongly. Regarding M6 stating “I am concerned that genetic testing may uncover a higher risk for other diseases in the future that I cannot prevent,” eight patients disagreed strongly, two disagreed a little, and only one agreed a little; there were four neutral responses. In response to M7 stating “I am concerned that my genetic information may be used to reduce or deny insurance coverage now or in the future,” five patients disagreed strongly, two disagreed a little, two agreed a little, and two agreed strongly; there were four neutral responses. These responses indicate wide variation among individuals in their perceptions of risks described in the consent. Participants tended to be most concerned about the biopsies associated with study participation and least concerned about a potential loss of confidentiality.

Motivations for participation (M8-9).

Two survey items focused on understanding motivations for study participation (Fig 1C; Data Supplement). All patients agreed strongly (n = 12) or a little (n = 3) with the statement that “genetic testing has a strong chance of helping my doctor find the best treatment for my cancer.” These responses contrasted with information provided during the consent process (Data Supplement). Virtually identical responses were obtained to the survey item stating “I want doctors to learn from my case so that they can help other cancer patients in the future,” with 13 patients agreeing strongly and two agreeing a little. These findings point to a near-uniform dual motivation for study participation: the potential for patients to obtain benefit themselves, which is significantly exaggerated compared with information provided at the time of consent, and the potential to benefit others.

Information from germline sequencing (M10-13).

All patients underwent either whole-exome sequencing (patients 1 to 12) or whole-genome sequencing (patients 13 to 15) of both germline (normal) and tumor DNA, and items M10 to M13 gauged perceptions regarding information from germline sequencing (Fig 1D; Data Supplement). Most patients agreed strongly (n = 10) or a little (n = 2) with item M10 stating “even though I have cancer, learning about my genetic risk for other diseases is still important to me” (one patient disagreed, and two were neutral). Almost all patients agreed strongly (n = 12) or a little (n = 2) with item M11 stating “the use of genetic testing to guide the treatment of my cancer is much more important to me than learning about my risk for other diseases in the future” (one patient gave a neutral response). Thirteen patients agreed strongly and two agreed a little with M12 stating “I am interested in genetic testing to learn whether genetic risk factors for cancer run in my family.” Twelve patients agreed strongly and two agreed a little with M13 stating “I want to know about genetic risk factors for cancer or other diseases in order to alert members of my family” (the one remaining patient was neutral). Collectively, all patients found some merit in germline testing.

Weighing uncertainty (M14-17).

Use of multidimensional molecular testing to infer drug susceptibilities for most cancers is in its infancy. Four survey items gauged patient views regarding if and how this information should be applied in their care (Fig 1E; Data Supplement). In response to M14 stating “only genetic tests that have been extensively validated in the lab should be used in efforts to find the best treatment for my cancer,” five patients agreed strongly, one agreed a little, seven neither agreed nor disagreed, and two disagreed strongly. In response to M15 stating “doctors should use the latest technologies to understand and treat my cancer, even if those technologies are not completely validated,” six patients agreed strongly, seven agreed a little, and two neither agreed nor disagreed. In response to M16 stating “I prefer a conservative approach to interpreting the genetic information from my tumor, even if it provides no guidance for treatment,” seven patients disagreed strongly, two disagreed a little, one agreed a little, and five neither agreed nor disagreed. Item M17 stated “if the genetic analysis of my tumor produces no strong leads for treatment, I would still like to be treated according to the next best lead, even if the supporting evidence is weak.” In response, nine patients agreed strongly, five agreed a little, and one remained neutral. Results suggest that patients want access to the latest technologies but have an expectation of diligence regarding the manner in which they are applied.

Responses at Baseline Versus Follow-Up (M1-M17)

Figure 2 compares the responses of all 10 patients who provided both baseline and follow-up surveys. As shown in the Data Supplement, these 10 participants had nearly identical baseline responses compared with the overall study population. Although several participants changed their responses at follow-up (Data Supplement), the overall distribution of most responses remained remarkably stable (Fig 2). Most prominent were declines in concerns related to undergoing multiple biopsies (M4) and increasing rejection of a conservative approach to test interpretation (M16). Notably, motivations for study participation were unchanged at follow-up.

Fig 2.

Fig 2.

Comparison of responses at baseline and follow-up for the 10 patients who completed both surveys. (A-E) Survey item categories. (A1-E1) Left graphs indicate numbers of patients agreeing strongly or a little with the indicated survey item; (A2-E2) middle graphs indicate numbers of patients disagreeing strongly or a little with the indicated survey item; (A3-E3) right graphs indicate numbers of patients neither agreeing nor disagreeing with the indicated survey item. Numbers at the top of each column denote numbers of patients providing the indicated responses. Survey items M1 to M17 are listed on the right.

Additional Items at Follow-Up (M18-M20)

Items M18 to M20 assessed how participation in ITOMIC-001 affected patient attitudes (Table 2). One patient “found the biopsies to be more difficult than anticipated” (M18), whereas seven of 10 disagreed strongly with this statement (two remained neutral). In response to M19 asking “in the past week: how much do you feel your genetic test result has made it harder to cope with your cancer,” two patients concurred a little, whereas the remaining eight concurred not at all. In response to M20 asking “in the past week: how much do you feel your genetic test result has made it easier to cope with your cancer,” two patients reported no improvement in coping, whereas the remaining eight reported at least some improvement (two a little, two somewhat, three a good deal, and one great deal).

DISCUSSION

Linking comprehensive molecular profiling of distinct metastatic sites to treatments and responses holds promise for improving our understanding of how cancers evolve and escape therapy1,3,4,9,10,17 and for advancing personalized medicine.6,45,46,56,57,65 Here, we describe patient views regarding novel features inherent in ITOMIC-001, including concerns about multiple biopsies, weighing of uncertainties inherent in complex molecular testing, the value attached to germline testing, and motivations for study participation and its impact on patient coping. Follow-up surveys allowed us to assess changes in perceptions after having spent time in the study. Although not directly assessed in our surveys, patients enrolled in ITOMIC-001 also had a much higher likelihood (67%) of accessing the drugs that were predicted to be effective than patients enrolled in molecular drug-matching trials.25,27,28,66,67

The most consistent responses pertained to the motivations for participation. All participants expressed an exaggerated expectation of benefit, which contrasts information that had been provided during our detailed consent process. This previously described overestimation of personal benefit has been hypothesized to reflect expressions of hope and optimism rather than a misunderstanding of facts presented at the time of consent.68-72 Patients seemed to be similarly motivated by a desire that their experiences benefit others, consistent with recent studies suggesting that altruism can be an important motivator for participation in clinical trials.73-75

Ranking lowest among patient concerns were the potential for loss of confidentiality and the possibility that incidental findings from germline testing might uncover genetic risk factors for diseases other than cancer. Somewhat greater levels of concern were attached to the prospect of undergoing multiple biopsies and the possibility that information from genetic testing may be used to reduce or deny insurance coverage now or in the future. Encouragingly, concerns regarding multiple biopsies fell substantially in follow-up surveys. Nevertheless, one patient found the biopsies to be somewhat more difficult than expected at follow-up, and one of the two patients who dropped out cited concerns regarding multiple biopsies as the reason. ITOMIC-001 differs from commonly known mandatory research biopsy drug trials in that the final decision about drug matching is made by the treating oncologist outside the ITOMIC-001 protocol.

Most participants seemed to understand the uncertainties inherent in using complex molecular testing for making treatment recommendations. Responses regarding the manner in which results of complex molecular testing should be applied in reaching treatment decisions varied according to how the question was asked. Collectively, however, responses suggest that most patients understood the difficulties inherent in interpreting results from complex molecular testing but nevertheless wanted the opportunity to have these findings thoughtfully applied in their care.

All patients underwent germline testing, and all wanted access to results to assess their risk for genetic diseases other than cancer and to assess family members’ risk for cancer or other genetic diseases. However, 14 of 15 participants agreed with the statement that “the use of genetic testing to guide the treatment of my cancer is much more important to me than learning about my risk for other diseases in the future.” Incidental genomic findings can be perceived as burdensome,48,52,54,55,76-78 particularly in individuals with a low tolerance for ambiguity54,55 or in hypothetical scenarios.79 However, patients with advanced cancer making real-world decisions tend to perceive this information as either useful information for family43,80 or seemingly insignificant in the context of their cancer.80

Our study is limited by its small size and incomplete follow-up. Many of our patients were particularly motivated and may not be representative of the general cancer population. It is encouraging that eight of 10 patients viewed participation in ITOMIC-001 as having helped them cope with their cancer. Although this relatively high degree of satisfaction may be related to a high rate of accessing drugs that were predicted to be effective,81 both patients who felt that participation had made coping with their cancer a little more difficult had received treatments on the basis of molecular results. Notably, these same two individuals also indicated that genetic test results had made it easier to cope with their cancer, and it will be important to understand the basis for these responses to further improve satisfaction levels among all study participants.

Although preliminary, our findings establish the feasibility of partnering with motivated patients in intensive clinical trials that seek to better understand how cancers evolve and escape therapy. In exchange, patients expect best efforts in interpreting results (however difficult) and in accessing the drugs from which they hope to benefit.

ACKNOWLEDGMENT

We thank the patients and their families and our research students Amanda Lu and Peter Lin.

Footnotes

Supported by South Sound CARE.

AUTHOR CONTRIBUTIONS

Conception and design: Nicole M. Kuderer, Sibel Blau, Francis Senecal, Vijayakrishna K. Gadi, Josh J. Carlson, C. Anthony Blau

Administrative support: Nicole M. Kuderer, Stephanie Parker

Provision of study materials or patients: Stephanie Parker, Vijayakrishna K. Gadi

Collection and assembly of data: Kimberly A. Burton, Francis Senecal, Stephanie Parker, Elisabeth Mahen, C. Anthony Blau

Data analysis and interpretation: Nicole M. Kuderer, Kimberly A. Burton, Sibel Blau, Vijayakrishna K. Gadi, David Veenstra, Gary H. Lyman, C. Anthony Blau

Manuscript writing: All authors

Final approval of manuscript: All authors

Accountable for all aspects of the work: All authors

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or po.ascopubs.org/site/ifc.

Nicole M. Kuderer

Consulting or Advisory Role: Janssen, Coherus Biosciences, Halozyme, G1 Therapeutics (I), Myriad Genetics

Research Funding: Amgen (I)

Travel, Accommodations, Expenses: Janssen, Coherus Bioscience

Kimberly A. Burton

Stock and Other Ownership Interests: Just Biotherapeutics (I)

Sibel Blau

Leadership: Northwest Medical Specialties

Stock and Other Ownership Interests: Northwest Medical Specialties

Research Funding: Northwest Medical Specialties

Expert Testimony: Northwest Medical Specialties

Travel, Accommodations, Expenses: Northwest Medical Specialties

Other Relationship: Northwest Medical Specialties

Francis Senecal

No relationship to disclose

Vijayakrishna K. Gadi

Stock and Other Ownership Interests: SEngine Precision Medicine

Research Funding: Genentech (Inst)

Stephanie Parker

No relationship to disclose

Elisabeth Mahen

No relationship to disclose

David Veenstra

Consulting or Advisory Role: Genentech, Jazz Pharmaceuticals, Relypsa

Josh J. Carlson

Consulting or Advisory Role: Pfizer, Genentech, Adaptive Biotechnologies, Neurocrine Biosciences

Travel, Accommodations, Expenses: Genentech

Gary H. Lyman

Consulting or Advisory Role: Halozyme, G1 Therapeutics, Coherus Biosciences

Research Funding: Amgen (Inst)

C. Anthony Blau

Employment: All4Cure

Leadership: All4Cure

Stock and Other Ownership Interests: All4Cure

Consulting or Advisory Role: Juno Therapeutics

Travel, Accommodations, Expenses: Novartis (I)

REFERENCES

  • 1.de Bruin EC, McGranahan N, Mitter R, et al. : Spatial and temporal diversity in genomic instability processes defines lung cancer evolution. Science 346:251-256, 2014 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Ding L, Ley TJ, Larson DE, et al. : Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing. Nature 481:506-510, 2012 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Gerlinger M, Horswell S, Larkin J, et al. : Genomic architecture and evolution of clear cell renal cell carcinomas defined by multiregion sequencing. Nat Genet 46:225-233, 2014 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Gerlinger M, Rowan AJ, Horswell S, et al. : Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 366:883-892, 2012 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Martinez P, Birkbak NJ, Gerlinger M, et al. : Parallel evolution of tumour subclones mimics diversity between tumours. J Pathol 230:356-364, 2013 [DOI] [PubMed] [Google Scholar]
  • 6.Priedigkeit N, Hartmaier RJ, Chen Y, et al. : Intrinsic subtype switching and acquired ERBB2/HER2 amplifications and mutations in breast cancer brain metastases. JAMA Oncol 3:666-671, 2017 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Sankin A, Hakimi AA, Mikkilineni N, et al. : The impact of genetic heterogeneity on biomarker development in kidney cancer assessed by multiregional sampling. Cancer Med 3:1485-1492, 2014 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Schilsky RL: Tumor heterogeneity as the foundation of personalized cancer treatment. Semin Oncol 38:171-172, 2011 [DOI] [PubMed] [Google Scholar]
  • 9.Shah SP, Roth A, Goya R, et al. : The clonal and mutational evolution spectrum of primary triple-negative breast cancers. Nature 486:395-399, 2012 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10. doi: 10.1371/journal.pmed.1002174. Hoadley KA, Siegel MB, Kanchi KL, et al: Tumor evolution in two patients with basal-like breast cancer: A retrospective genomics study of multiple metastases. PLoS Med 13:e1002174, 2016 [Erratum: PLoS Med 14:e1002222, 2017] [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Fribbens C, O’Leary B, Kilburn L, et al. : Plasma ESR1 mutations and the treatment of estrogen receptor–positive advanced breast cancer. J Clin Oncol 34:2961-2968, 2016 [DOI] [PubMed] [Google Scholar]
  • 12.Gorre ME, Mohammed M, Ellwood K, et al. : Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 293:876-880, 2001 [DOI] [PubMed] [Google Scholar]
  • 13.Katayama R, Shaw AT, Khan TM, et al. : Mechanisms of acquired crizotinib resistance in ALK-rearranged lung cancers. Sci Transl Med 4:120ra17, 2012 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Schiavon G, Hrebien S, Garcia-Murillas I, et al. : Analysis of ESR1 mutation in circulating tumor DNA demonstrates evolution during therapy for metastatic breast cancer. Sci Transl Med 7:313ra182, 2015 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Wang P, Bahreini A, Gyanchandani R, et al. : Sensitive detection of mono- and polyclonal ESR1 mutations in primary tumors, metastatic lesions, and cell-free DNA of breast cancer patients. Clin Cancer Res 22:1130-1137, 2016 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Gerlinger M, Norton L, Swanton C: Acquired resistance to crizotinib from a mutation in CD74-ROS1. N Engl J Med 369:1172-1173, 2013 [DOI] [PubMed] [Google Scholar]
  • 17.Jankowitz RC, Oesterreich S, Lee AV, et al. : New strategies in metastatic hormone receptor-positive breast cancer: Searching for biomarkers to tailor endocrine and other targeted therapies. Clin Cancer Res 23:1126-1131, 2017 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Borden EC, Raghavan D: Personalizing medicine for cancer: The next decade. Nat Rev Drug Discov 9:343-344, 2010 [DOI] [PubMed] [Google Scholar]
  • 19.Hamburg MA, Collins FS: The path to personalized medicine. N Engl J Med 363:301-304, 2010 [DOI] [PubMed] [Google Scholar]
  • 20.Jardim DL, Schwaederle M, Wei C, et al. : Impact of a biomarker-based strategy on oncology drug development: A meta-analysis of clinical trials leading to FDA approval. J Natl Cancer Inst 15:107, 2015 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Schilsky RL: Personalized medicine in oncology: The future is now. Nat Rev Drug Discov 9:363-366, 2010 [DOI] [PubMed] [Google Scholar]
  • 22.Schilsky RL: Implementing personalized cancer care. Nat Rev Clin Oncol 11:432-438, 2014 [DOI] [PubMed] [Google Scholar]
  • 23.Schwaederle M, Zhao M, Lee JJ, et al. : Impact of precision medicine in diverse cancers: A meta-analysis of phase II clinical trials. J Clin Oncol 33:3817-3825, 2015 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Schwaederle M, Zhao M, Lee JJ, et al. : Association of biomarker-based treatment strategies with response rates and progression-free survival in refractory malignant neoplasms: A meta-analysis. JAMA Oncol 2:1452-1459, 2016 [DOI] [PubMed] [Google Scholar]
  • 25.McNeil C: NCI-MATCH launch highlights new trial design in precision-medicine era. J Natl Cancer Inst 3:107, 2015 [DOI] [PubMed] [Google Scholar]
  • 26.Mullard A: NCI-MATCH trial pushes cancer umbrella trial paradigm. Nat Rev Drug Discov 14:513-515, 2015 [DOI] [PubMed] [Google Scholar]
  • 27.Le Tourneau C, Delord JP, Gonçalves A, et al. : Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (SHIVA): A multicentre, open-label, proof-of-concept, randomised, controlled phase 2 trial. Lancet Oncol 16:1324-1334, 2015 [DOI] [PubMed] [Google Scholar]
  • 28.Stockley TL, Oza AM, Berman HK, et al. : Molecular profiling of advanced solid tumors and patient outcomes with genotype-matched clinical trials: The Princess Margaret IMPACT/COMPACT trial. Genome Med 8:109, 2016 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Deluche E, Onesti E, Andre F: Precision medicine for metastatic breast cancer. Am Soc Clin Oncol Educ Book e2-e7, 2015 [DOI] [PubMed] [Google Scholar]
  • 30.Andre F, Delaloge S, Soria JC: Biology-driven phase II trials: What is the optimal model for molecular selection? J Clin Oncol 29:1236-1238, 2011 [DOI] [PubMed] [Google Scholar]
  • 31.Dieci MV, Smutná V, Scott V, et al. : Whole exome sequencing of rare aggressive breast cancer histologies. Breast Cancer Res Treat 156:21-32, 2016 [DOI] [PubMed] [Google Scholar]
  • 32.Tursz T, Andre F, Lazar V, et al. : Implications of personalized medicine: Perspective from a cancer center. Nat Rev Clin Oncol 8:177-183, 2011 [DOI] [PubMed] [Google Scholar]
  • 33.Uzilov AV, Ding W, Fink MY, et al. : Development and clinical application of an integrative genomic approach to personalized cancer therapy. Genome Med 8:62, 2016 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Evans JP, Berg JS: Next-generation DNA sequencing, regulation, and the limits of paternalism: The next challenge. JAMA 306:2376-2377, 2011 [DOI] [PubMed] [Google Scholar]
  • 35.Evans JP, Watson MS: Genetic testing and FDA regulation: Overregulation threatens the emergence of genomic medicine. JAMA 313:669-670, 2015 [DOI] [PubMed] [Google Scholar]
  • 36.ACMG Board of Directors : ACMG policy statement: Updated recommendations regarding analysis and reporting of secondary findings in clinical genome-scale sequencing. Genet Med 17:68-69, 2015 [DOI] [PubMed] [Google Scholar]
  • 37.Smith LA, Douglas J, Braxton AA, et al. : Reporting incidental findings in clinical whole exome sequencing: Incorporation of the 2013 ACMG recommendations into current practices of genetic counseling. J Genet Couns 24:654-662, 2015 [DOI] [PubMed] [Google Scholar]
  • 38.Scheuner MT, Peredo J, Benkendorf J, et al. : Reporting genomic secondary findings: ACMG members weigh in. Genet Med 17:27-35, 2015 [DOI] [PubMed] [Google Scholar]
  • 39.Koay PP, Sharp RR: Managing expectational language: Translational genetic professionals consider the clinical potential of next-generation sequencing technologies. New Genet Soc 33:126-148, 2014 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Berg JS, Amendola LM, Eng C, et al. : Processes and preliminary outputs for identification of actionable genes as incidental findings in genomic sequence data in the Clinical Sequencing Exploratory Research Consortium. Genet Med 15:860-867, 2013 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41.Berg JS, Khoury MJ, Evans JP: Deploying whole genome sequencing in clinical practice and public health: Meeting the challenge one bin at a time. Genet Med 13:499-504, 2011 [DOI] [PubMed] [Google Scholar]
  • 42.Catenacci DV, Amico AL, Nielsen SM, et al. : Tumor genome analysis includes germline genome: Are we ready for surprises? Int J Cancer 136:1559-1567, 2015 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43.Pinheiro APM, Pocock RH, Switchenko JM, et al. : Discussing molecular testing in oncology care: Comparing patient and physician information preferences. Cancer 123:1610-1616, 2017 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 44.Blazer KR, Nehoray B, Solomon I, et al. : Next-generation testing for cancer risk: Perceptions, experiences, and needs among early adopters in community healthcare settings. Genet Test Mol Biomarkers 19:657-665, 2015 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45.Lyman GH, Moses HL: Biomarker tests for molecularly targeted therapies: The key to unlocking precision medicine. N Engl J Med 375:4-6, 2016 [DOI] [PubMed] [Google Scholar]
  • 46.Lyman GH, Moses HL: Biomarker tests for molecularly targeted therapies: Laying the foundation and fulfilling the dream. J Clin Oncol 34:2061-2066, 2016 [DOI] [PubMed] [Google Scholar]
  • 47.Zawati MH, Parry D, Thorogood A, et al. : Reporting results from whole-genome and whole-exome sequencing in clinical practice: A proposal for Canada? J Med Genet 51:68-70, 2014 [DOI] [PubMed] [Google Scholar]
  • 48. doi: 10.1007/s10897-014-9804-6. Khan CM, Rini C, Bernhardt BA, et al: How can psychological science inform research about genetic counseling for clinical genomic sequencing? J Genet Couns 24:193-204, 2015 [Erratum: J Genet Couns 24:372, 2015] [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 49.Yu JH, Crouch J, Jamal SM, et al. : Attitudes of African Americans toward return of results from exome and whole genome sequencing. Am J Med Genet A 161A:1064-1072, 2013 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 50.Rogith D, Yusuf RA, Hovick SR, et al. : Patient knowledge and information-seeking about personalized cancer therapy. Int J Med Inform 88:52-57, 2016 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 51.Issa AM, Tufail W, Hutchinson J, et al. : Assessing patient readiness for the clinical adoption of personalized medicine. Public Health Genomics 12:163-169, 2009 [DOI] [PubMed] [Google Scholar]
  • 52.Pellegrini I, Rapti M, Extra JM, et al. : Tailored chemotherapy based on tumour gene expression analysis: Breast cancer patients’ misinterpretations and positive attitudes. Eur J Cancer Care (Engl) 21:242-250, 2012 [DOI] [PubMed] [Google Scholar]
  • 53.Facio FM, Eidem H, Fisher T, et al. : Intentions to receive individual results from whole-genome sequencing among participants in the ClinSeq study. Eur J Hum Genet 21:261-265, 2013 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 54.Taber JM, Klein WM, Ferrer RA, et al. : Perceived ambiguity as a barrier to intentions to learn genome sequencing results. J Behav Med 38:715-726, 2015 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 55.Taber JM, Klein WM, Ferrer RA, et al. : Dispositional optimism and perceived risk interact to predict intentions to learn genome sequencing results. Health Psychol 34:718-728, 2015 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 56.Blau CA: Can intensive longitudinal monitoring of individuals advance cancer research? Oncologist 17:587-589, 2012 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 57.Blau CA, Liakopoulou E: Can we deconstruct cancer, one patient at a time? Trends Genet 29:6-10, 2013 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 58.Peppercorn J, Shapira I, Collyar D, et al. : Ethics of mandatory research biopsy for correlative end points within clinical trials in oncology. J Clin Oncol 28:2635-2640, 2010 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 59. doi: 10.1001/jamaoncol.2016.4983. Kuderer NM, Burton KA, Blau S, et al: Comparison of 2 commercially available next-generation sequencing platforms in oncology. JAMA Oncol 3:996-998, 2017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 60.Chae YK, Davis AA, Carneiro BA, et al. : Concordance between genomic alterations assessed by next-generation sequencing in tumor tissue or circulating cell-free DNA. Oncotarget 7:65364-65373, 2016 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 61.Jovelet C, Ileana E, Le Deley MC, et al. : Circulating cell-free tumor DNA analysis of 50 genes by next-generation sequencing in the prospective MOSCATO trial. Clin Cancer Res 22:2960-2968, 2016 [DOI] [PubMed] [Google Scholar]
  • 62.Couraud S, Vaca-Paniagua F, Villar S, et al. : Noninvasive diagnosis of actionable mutations by deep sequencing of circulating free DNA in lung cancer from never-smokers: A proof-of-concept study from BioCAST/IFCT-1002. Clin Cancer Res 20:4613-4624, 2014 [DOI] [PubMed] [Google Scholar]
  • 63.Blau CA, Ramirez AB, Blau S, et al. : A distributed network for intensive longitudinal monitoring in metastatic triple-negative breast cancer. J Natl Compr Canc Netw 14:8-17, 2016 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 64.Likert R: A technique for the measurement of attitudes. Arch Psychol 140:1-55, 1932 [Google Scholar]
  • 65.Arnedos M, Vielh P, Soria JC, et al. : The genetic complexity of common cancers and the promise of personalized medicine: Is there any hope? J Pathol 232:274-282, 2014 [DOI] [PubMed] [Google Scholar]
  • 66.Colwell J: NCI-MATCH trial draws strong interest. Cancer Discov 6:334, 2016 [DOI] [PubMed] [Google Scholar]
  • 67.André F, Bachelot T, Commo F, et al. : Comparative genomic hybridisation array and DNA sequencing to direct treatment of metastatic breast cancer: A multicentre, prospective trial (SAFIR01/UNICANCER). Lancet Oncol 15:267-274, 2014 [DOI] [PubMed] [Google Scholar]
  • 68.Sulmasy DP, Astrow AB, He MK, et al. : The culture of faith and hope: Patients’ justifications for their high estimations of expected therapeutic benefit when enrolling in early phase oncology trials. Cancer 116:3702-3711, 2010 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 69.Jansen LA, Mahadevan D, Appelbaum PS, et al. : Dispositional optimism and therapeutic expectations in early-phase oncology trials. Cancer 122:1238-1246, 2016 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 70.Weinfurt KP, Seils DM, Tzeng JP, et al. : Expectations of benefit in early-phase clinical trials: Implications for assessing the adequacy of informed consent. Med Decis Making 28:575-581, 2008 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 71.Weinfurt KP, Castel LD, Li Y, et al. : The correlation between patient characteristics and expectations of benefit from phase I clinical trials. Cancer 98:166-175, 2003 [DOI] [PubMed] [Google Scholar]
  • 72.Weinfurt KP, Seils DM, Lin L, et al. : Research participants’ high expectations of benefit in early-phase oncology trials: Are we asking the right question? J Clin Oncol 30:4396-4400, 2012 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 73.Moore S: A need to try everything: Patient participation in phase I trials. J Adv Nurs 33:738-747, 2001 [DOI] [PubMed] [Google Scholar]
  • 74.Wendler D, Krohmal B, Emanuel EJ, et al. : Why patients continue to participate in clinical research. Arch Intern Med 168:1294-1299, 2008 [DOI] [PubMed] [Google Scholar]
  • 75.Sanderson SC, Linderman MD, Suckiel SA, et al. : Motivations, concerns and preferences of personal genome sequencing research participants: Baseline findings from the HealthSeq project. Eur J Hum Genet 24:14-20, 2016 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 76.Metcalfe KA, Poll A, Llacuachaqui M, et al. : Patient satisfaction and cancer-related distress among unselected Jewish women undergoing genetic testing for BRCA1 and BRCA2. Clin Genet 78:411-417, 2010 [DOI] [PubMed] [Google Scholar]
  • 77.Sanderson SC, Linderman MD, Zinberg R, et al. : How do students react to analyzing their own genomes in a whole-genome sequencing course? Outcomes of a longitudinal cohort study. Genet Med 17:866-874, 2015 [DOI] [PubMed] [Google Scholar]
  • 78.Diaz VA, Mainous AG, III, Gavin JK, et al. : Racial differences in attitudes toward personalized medicine. Public Health Genomics 17:1-6, 2014 [DOI] [PubMed] [Google Scholar]
  • 79. Gray SW, Hicks-Courant K, Lathan CS, et al: Attitudes of patients with cancer about personalized medicine and somatic genetic testing. J Oncol Pract 8:329-335, 2 p following 335, 2012. [DOI] [PMC free article] [PubMed]
  • 80.Miller FA, Hayeems RZ, Bytautas JP, et al. : Testing personalized medicine: Patient and physician expectations of next-generation genomic sequencing in late-stage cancer care. Eur J Hum Genet 22:391-395, 2014 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 81. doi: 10.1001/jamaoncol.2016.3283. Zikmund-Fisher BJ: When “actionable” genomic sequencing results cannot be acted upon. JAMA Oncol 3:891-892, 2017. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from JCO Precision Oncology are provided here courtesy of American Society of Clinical Oncology

RESOURCES