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Cited by 1,369Breast Cancer Treatment StudiesAdvanced Breast Cancer TherapiesHER2/EGFR in Cancer Research

5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5)

Open access
Cardoso, F., Paluch-Shimon, S., Senkus, E., Curigliano, G., Aapro, M.S., André, F., Barrios, C.H., Bergh, J. +37 more·2020·Annals of Oncology
DOI 10.1016/j.annonc.2020.09.010PMC PMC7510449
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Abstract

For the purpose of advanced breast cancer (ABC) guidelines, ABC comprises both inoperable locally advanced breast cancer (LABC) and metastatic breast cancer (MBC).1,2 Advanced/metastatic breast cancer remains a virtually incurable disease, with a median overall survival (OS) of about 3 years and a 5-year survival rate of around 25%,3,4 even in countries without major accessibility problems. Survival is strongly related to breast cancer subtype, with the major advances seen in human epidermal growth factor receptor 2 (HER2)-positive ABC.

Integrity signals

Registry

Crossref · 10.1016/j.annonc.2020.09.010

Cites

142 of 142 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

48 of 132 cited sources checked · 21 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    CDK4/6 inhibitors plus endocrine therapy are standard of care for ER-positive/HER2-negative ABC.

    “The last 2 years have seen the establishment of cyclin-dependent kinase (CDK)4/6 inhibitors combined with endocrine therapy (ET) as the standard of care for ER-positive/HER2-negative ABC”
    Quote in the paperSubstantial claim4 of 10 sources checked
    • cites [36] Im, 2019, Overall survival with ribociclib plus endocrine therapy in breast cancer, N Engl J Med source
    • cites [37] Slamon, 2020, Overall survival with ribociclib plus fulvestrant in advanced breast cancer, N Engl J Med source

      The paper’s Abstract (page not supplied) says CDK4/6 inhibitors have improved outcomes in advanced breast cancer and that three are approved for hormone-receptor-positive, HER2-negative disease. The Discussion (page not supplied) says its findings may support considering ribociclib plus fulvestrant as initial therapy. These passages support the clinical role of the combination, but do not establish that CDK4/6 inhibitors plus endocrine therapy became the standard of care in the stated two-year period. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [38] Slamon, 2018, Phase III randomized study of ribociclib and fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: MONALEESA-3, J Clin Oncol source
    • cites [39] Sledge, 2019, The effect of abemaciclib plus fulvestrant on overall survival in hormone receptor-positive, erbb2-negative breast cancer that progressed on endocrine therapy-MONARCH 2: a randomized clinical trial, JAMA Oncol source
      Experimental — accuracy not yet measured
    • cites [40] Sledge, 2017, MONARCH 2: abemaciclib in combination with fulvestrant in women with HR+/HER2- advanced breast cancer who had progressed while receiving endocrine therapy, J Clin Oncol source
    • cites [41] Tripathy, 2018, Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial, Lancet Oncol source
    • cites [42] Tripathy, 2018, Cancer Res

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [43] Finn, 2016, Palbociclib and letrozole in advanced breast cancer, N Engl J Med source
    • cites [44] Hortobagyi, 2016, Ribociclib as first-line therapy for HR-positive, advanced breast cancer, N Engl J Med source

      The Discussion reports longer progression-free survival with ribociclib plus letrozole than with letrozole alone in postmenopausal women receiving first-line treatment for HR-positive, HER2-negative advanced breast cancer. The paper supports the combination’s efficacy, but does not establish that CDK4/6 inhibitors as a class combined with endocrine therapy had become the standard of care. Its introduction instead identifies endocrine therapy as the standard of care at the time. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [45] Rugo, 2019, Palbociclib plus letrozole as first-line therapy in estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer with extended follow-up, Breast Cancer Res Treat source
      Experimental — accuracy not yet measured
  • Premisecitation

    Survival ranges are more accurate than a single expected survival estimate.

    “Ranges for survival scenarios are also more accurate than a single point estimate of expected survival.16 , 32 , 33”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [16] Smith-Uffen, 2020, Estimating survival in advanced cancer: a comparison of estimates made by oncologists and patients, Support Care Cancer source
    • cites [32] Stockler, 2006, Disarming the guarded prognosis: predicting survival in newly referred patients with incurable cancer, Br J Cancer source
    • cites [33] Kiely, 2013, The median informs the message: accuracy of individualized scenarios for survival time based on oncologists' estimates, J Clin Oncol source
  • Premisecitation

    CDK4/6 inhibitors plus endocrine therapy confer OS benefit in first- and second-line settings for ER-positive/HER2-negative ABC.

    “in view of the OS benefit seen in several trials,36, 37, 38, 39, 40, 41, 42 both in the first- and second-line settings”
    Quote in the paperSubstantial claim2 of 7 sources checked
    • cites [36] Im, 2019, Overall survival with ribociclib plus endocrine therapy in breast cancer, N Engl J Med source
    • cites [37] Slamon, 2020, Overall survival with ribociclib plus fulvestrant in advanced breast cancer, N Engl J Med source
    • cites [38] Slamon, 2018, Phase III randomized study of ribociclib and fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: MONALEESA-3, J Clin Oncol source
    • cites [39] Sledge, 2019, The effect of abemaciclib plus fulvestrant on overall survival in hormone receptor-positive, erbb2-negative breast cancer that progressed on endocrine therapy-MONARCH 2: a randomized clinical trial, JAMA Oncol source
      Experimental — accuracy not yet measured
    • cites [40] Sledge, 2017, MONARCH 2: abemaciclib in combination with fulvestrant in women with HR+/HER2- advanced breast cancer who had progressed while receiving endocrine therapy, J Clin Oncol source
    • cites [41] Tripathy, 2018, Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial, Lancet Oncol source
    • cites [42] Tripathy, 2018, Cancer Res

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Premisecitation

    Many patients desire more prognostic information than clinicians typically expect.

    “Most patients want considerably more information than many healthcare professionals expect, but the type and amount of information sought should be clarified.23”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [23] Jenkins, 2001, Information needs of patients with cancer: results from a large study in UK cancer centres, Br J Cancer source
  • Premisecitation

    BROCADE3 demonstrated a progression-free survival benefit favouring the veliparib arm, with median progression-free survival 14.5 vs 12.6 months (HR 0.71; 95% CI 0.57-0.88, P=0.002).

    “The study demonstrated a PFS benefit favouring the veliparib arm, with a median PFS of 14.5 versus 12.6 months (HR 0.71; 95% CI 0.57-0.88, P = 0.002)”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [79] Dieras, 2019, Phase 3 study of veliparib with carboplatin and paclitaxel in HER2-negative advanced/metastatic gBRCA-associated breast cancer, Ann Oncol source
  • May combine two claims. 29
  • Classified as probably not a substantial claim. 8
  • The quote only partly states this claim. 1

  • May combine two claims.

    Premisecitation

    Patients with advanced cancer commonly misunderstand their prognosis, and such misunderstandings are linked to more futile treatment.

    “Misunderstandings about prognosis are common16, 17, 18 and are associated with increased exposure to futile treatments.19, 20, 21, 22”
    Quote in the paperSubstantial claim2 of 7 sources checked
    • cites [16] Smith-Uffen, 2020, Estimating survival in advanced cancer: a comparison of estimates made by oncologists and patients, Support Care Cancer source
    • cites [17] Hagerty, 2005, Communicating prognosis in cancer care: a systematic review of the literature, Ann Oncol source
    • cites [18] Fried, 2003, Prognosis communication in serious illness: perceptions of older patients, caregivers, and clinicians, J Am Geriatr Soc source
    • cites [19] Mack, 2012, Associations between end-of-life discussion characteristics and care received near death: a prospective cohort study, J Clin Oncol source

      The Abstract reports that earlier end-of-life discussions were associated with less aggressive care in patients with stage IV lung or colorectal cancer. But the Discussion says the study did not assess discussion content, and its care measures could not distinguish beneficial from ineffective treatment. It therefore does not establish that misunderstandings about prognosis were associated with futile treatment. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [20] Wright, 2008, Associations between end-of-life discussions, patient mental health, medical care near death, and caregiver bereavement adjustment, JAMA source

      The Discussion (page unavailable) says cancer patients frequently misunderstand or fail to recall prognostic discussions. The Results (Medical care at the end-of-life; page unavailable) associate reported end-of-life discussions with fewer aggressive interventions near death, but the study does not establish that prognostic misunderstandings themselves are associated with greater exposure to treatment, or characterize those treatments as futile. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [21] Weeks, 1998, Relationship between cancer patients' predictions of prognosis and their treatment preferences, JAMA source
    • cites [22] Pronzato, 1994, What do advanced cancer patients know of their disease? A report from Italy, Support Care Cancer source

  • May combine two claims.

    Premisecitation

    CDK4/6 inhibitors plus endocrine therapy provide substantial PFS benefit and a favorable toxicity profile.

    “substantial PFS benefit and good toxicity profile.36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57”
    Quote in the paperSubstantial claim4 of 10 sources checked
    • cites [36] Im, 2019, Overall survival with ribociclib plus endocrine therapy in breast cancer, N Engl J Med source
    • cites [37] Slamon, 2020, Overall survival with ribociclib plus fulvestrant in advanced breast cancer, N Engl J Med source

      The Progression-free Survival section reports a substantial benefit for ribociclib plus fulvestrant over placebo plus fulvestrant in patients with advanced breast cancer. The Adverse Events section reports no new safety signals, but adverse events were more frequent with ribociclib, including grade 3 or 4 neutropenia in 57.1% versus 0.8%; it does not establish the claimed good toxicity profile. The trial also addresses this specific combination, not CDK4/6 inhibitors as a class. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [38] Slamon, 2018, Phase III randomized study of ribociclib and fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: MONALEESA-3, J Clin Oncol source
    • cites [39] Sledge, 2019, The effect of abemaciclib plus fulvestrant on overall survival in hormone receptor-positive, erbb2-negative breast cancer that progressed on endocrine therapy-MONARCH 2: a randomized clinical trial, JAMA Oncol source

      In Other Exploratory End Points (page not provided), abemaciclib plus fulvestrant improved median PFS to 16.9 months versus 9.3 months with placebo plus fulvestrant. The Discussion (page not provided) describes its safety profile as generally tolerable and manageable. The paper supports these points for abemaciclib plus fulvestrant in the studied patients, but not for CDK4/6 inhibitors plus endocrine therapy as a class. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [40] Sledge, 2017, MONARCH 2: abemaciclib in combination with fulvestrant in women with HR+/HER2- advanced breast cancer who had progressed while receiving endocrine therapy, J Clin Oncol source
    • cites [41] Tripathy, 2018, Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial, Lancet Oncol source
    • cites [42] Tripathy, 2018, Cancer Res

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [43] Finn, 2016, Palbociclib and letrozole in advanced breast cancer, N Engl J Med source
    • cites [44] Hortobagyi, 2016, Ribociclib as first-line therapy for HR-positive, advanced breast cancer, N Engl J Med source

      The Discussion reports significantly longer progression-free survival with ribociclib plus letrozole and describes its adverse-event profile as acceptable for most patients. But this trial studied one CDK4/6 inhibitor with one endocrine therapy in postmenopausal women with HR-positive, HER2-negative advanced breast cancer; it does not establish the same benefit and toxicity profile for all CDK4/6 inhibitor–endocrine therapy combinations. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [45] Rugo, 2019, Palbociclib plus letrozole as first-line therapy in estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer with extended follow-up, Breast Cancer Res Treat source

  • May combine two claims.

    Premisecitation

    In stable brain metastases, tucatinib combination reduced CNS progression or death risk by 69%; in active brain metastases, objective response rate was 47% and death risk was reduced by 51%.

    “Importantly, a reduction in the risk of CNS progression or death by 69% was observed in patients with stable brain metastases, while a confirmed objective response rate of 47% and a reduced risk of death by 51% were observed in patients with active brain metastases.63”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [63] Lin, 2020, Intracranial efficacy and survival with tucatinib plus trastuzumab and capecitabine for previously treated HER2-positive breast cancer with brain metastases in the HER2CLIMB trial, J Clin Oncol source

      The Results sections for stable and active brain metastases report the 69% reduction in CNS progression or death and the 51% reduction in death, respectively. The Results also report a 47.3% confirmed intracranial response rate, but only among patients with active brain metastases who had measurable intracranial disease at baseline; the claim omits that restriction. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    In the intention-to-treat population of IMpassion-130, there was no significant overall survival benefit with atezolizumab; median overall survival was 21.3 vs 17.6 months (HR 0.84; 95% CI 0.69-1.02, P=0.08).

    “In the ITT population, there was no significant benefit in OS with the addition of atezolizumab; median OS was 21.3 months versus 17.6 months (HR 0.84; 95% CI 0.69-1.02, P = 0.08).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [68] Schmid, 2018, Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer, N Engl J Med source

  • May combine two claims.

    Premisecitation

    CDK4/6 inhibitors can be combined with an aromatase inhibitor or fulvestrant and are effective across de novo or recurrent ABC, first or second line, primary or secondary resistance, postmenopausal and premenopausal women (with ovarian suppression/ablation), and men.

    “These agents can be combined with an aromatase inhibitor (AI) or fulvestrant, and are effective in de novo or recurrent ABC, in first or second line, in cases of primary or secondary resistance, in postmenopausal and premenopausal women (the latter with ovarian function suppression/ablation), and in men (preferably with a luteinising hormone-releasing hormone agonist).”
    Quote in the paperSubstantial claim4 of 10 sources checked
    • cites [36] Im, 2019, Overall survival with ribociclib plus endocrine therapy in breast cancer, N Engl J Med source
    • cites [37] Slamon, 2020, Overall survival with ribociclib plus fulvestrant in advanced breast cancer, N Engl J Med source

      Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured
    • cites [38] Slamon, 2018, Phase III randomized study of ribociclib and fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: MONALEESA-3, J Clin Oncol source
    • cites [39] Sledge, 2019, The effect of abemaciclib plus fulvestrant on overall survival in hormone receptor-positive, erbb2-negative breast cancer that progressed on endocrine therapy-MONARCH 2: a randomized clinical trial, JAMA Oncol source

      Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured
    • cites [40] Sledge, 2017, MONARCH 2: abemaciclib in combination with fulvestrant in women with HR+/HER2- advanced breast cancer who had progressed while receiving endocrine therapy, J Clin Oncol source
    • cites [41] Tripathy, 2018, Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial, Lancet Oncol source
    • cites [42] Tripathy, 2018, Cancer Res

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [43] Finn, 2016, Palbociclib and letrozole in advanced breast cancer, N Engl J Med source
    • cites [44] Hortobagyi, 2016, Ribociclib as first-line therapy for HR-positive, advanced breast cancer, N Engl J Med source

      Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured
    • cites [45] Rugo, 2019, Palbociclib plus letrozole as first-line therapy in estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer with extended follow-up, Breast Cancer Res Treat source

      Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Trastuzumab deruxtecan carried a 13.6% risk of ILD/pneumonitis, fatal in 2.2% of cases.

    “Trastuzumab deruxtecan was associated with a 13.6% risk of interstitial lung disease (ILD)/pneumonitis, fatal in 2.2% of cases, which needed appropriate and rapid diagnosis and treatment.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [64] Modi, 2020, Trastuzumab deruxtecan in previously treated HER2-positive breast cancer, N Engl J Med source

      The Results > Safety passage reports ILD in 25 patients (13.6%) and four ILD-attributed deaths (2.2% of all treated patients). The claim's “fatal in 2.2% of cases” is imprecise: if “cases” means patients who developed ILD, the fatal proportion was four of 25, not 2.2%. The Discussion supports early detection and prompt intervention. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Interpretationreasoning

    PD-L1 status by SP142 is the companion test for atezolizumab plus a taxane in first-line triple-negative advanced breast cancer, with a cut-off of 1% positive staining on immune cells.

    “Thus, PD-L1 status by SP142 is the companion test for the use of atezolizumab in combination with a taxane for first-line therapy in triple-negative ABC, with a cut-off of 1% positive staining on immune cells.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [68] Schmid, 2018, Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer, N Engl J Med source

      Trial Design and Procedures (page not provided) defines PD-L1 positivity as expression on tumor-infiltrating immune cells covering at least 1% of tumor area, and the Discussion reports first-line benefit with atezolizumab plus nab-paclitaxel. The paper does not establish SP142 as a companion test in its trial description; SP142 appears in a reference to a *complementary* diagnostic assay. The claim also broadens nab-paclitaxel to taxanes generally and describes the cutoff as 1% of immune cells staining positive rather than 1% of tumor area. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Trastuzumab deruxtecan produced a 60.6% response rate (95% CI 53.4-68.0) and median PFS of 16.4 months (95% CI 12.7-not reached) in heavily pretreated patients (median six lines; range 2-27; including trastuzumab and T-DM1).

    “Trastuzumab deruxtecan (DS-8201), an ADC composed of trastuzumab, a cleavable tetrapeptide-based linker and a cytotoxic topoisomerase I inhibitor, demonstrated a response rate of 60.6% (95% CI 53.4-68.0) and an unprecedented median PFS of 16.4 months (95% CI 12.7—not reached) in a phase II study of heavily pretreated patients (median six lines, range 2-27 lines, including trastuzumab and T-DM1).64”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [64] Modi, 2020, Trastuzumab deruxtecan in previously treated HER2-positive breast cancer, N Engl J Med source

      Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Alpelisib plus fulvestrant caused substantially more toxicity, including hyperglycaemia, rash, GI complaints, and fatigue, with dose reductions/interruptions in about 70% and discontinuations in 25%.

    “Toxicity was substantially increased in the alpelisib arm, especially hyperglycaemia, rash, gastrointestinal (GI) complaints (nausea, vomiting, loss of appetite, mucositis, diarrhoea) and fatigue, which lead to dose reductions/interruptions in around 70% of patients and discontinuations in 25%.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [58] André, 2019, Alpelisib for PIK3CA-mutated, hormone receptor-positive advanced breast cancer, N Engl J Med source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Melatonin may be used to treat sleep disturbances.

    “Sleep disturbances may be treated with melatonin.122 , 123”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [122] Chen, 2014, A randomized, placebo-controlled trial of melatonin on breast cancer survivors: impact on sleep, mood, and hot flashes, Breast Cancer Res Treat source
    • cites [123] Innominato, 2016, The effect of melatonin on sleep and quality of life in patients with advanced breast cancer, Support Care Cancer source

  • Classified as probably not a substantial claim.

    Premisecitation

    Mind-body interventions, physical training and cognitive behavioural therapy are effective non-pharmacological treatment options for menopausal symptoms.

    “For menopausal symptoms in general, mind-body interventions, physical training and cognitive behavioural therapy should be recommended as effective non-pharmacological treatment options.113, 114, 115, 116, 117”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [113] Duijts, 2012, Efficacy of cognitive behavioral therapy and physical exercise in alleviating treatment-induced menopausal symptoms in patients with breast cancer: results of a randomized, controlled, multicenter trial, J Clin Oncol source
    • cites [114] Mann, 2012, Cognitive behavioural treatment for women who have menopausal symptoms after breast cancer treatment (MENOS 1): a randomised controlled trial, Lancet Oncol source

      The Discussion (page unavailable) reports sustained benefits from CBT for hot flushes and night sweats in women after breast cancer treatment and calls it an effective treatment option for that group. It mentions only preliminary findings from a separate CBT-and-exercise trial; it does not establish physical training or mind-body interventions as independently effective, or extend its recommendation to menopausal symptoms in general. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [115] Stefanopoulou, 2017, Mind-body interventions for vasomotor symptoms in healthy menopausal women and breast cancer survivors. A systematic review, J Psychosom Obstet Gynaecol source

      The Conclusion (p. 15) supports recommending CBT for vasomotor symptoms and reports more consistent evidence for relaxation therapies. It also says evidence is insufficient to treat several other mind-body interventions as evidence-based options. The review does not establish physical training as effective, and its findings concern vasomotor symptoms rather than menopausal symptoms in general. (LLM, conf=0.90)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Evidence indicates that some oncologists are overly optimistic about anticancer treatment survival benefits, while others are overly pessimistic about supportive care benefits.

    “there is evidence that some oncologists are overly optimistic about survival benefits from anticancer treatments while others are unduly nihilistic about the benefits of good quality supportive care.34”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [34] Fallowfield, 2017, Therapeutic aims of drugs offering only progression-free survival are misunderstood by patients, and oncologists may be overly optimistic about likely benefits, Support Care Cancer source

  • Classified as probably not a substantial claim.

    Premisecitation

    For patients seeking quantitative life-expectancy information, giving worst-case, typical, and best-case ranges is more helpful and hopeful than a single median survival estimate.

    “For patients wanting quantitative information on life expectancy, providing ranges for worst-case, typical and best-case scenarios is more helpful and conveys more hope than providing a single point estimate of median survival.31”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [31] Kiely, 2013, Using scenarios to explain life expectancy in advanced cancer: attitudes of people with a cancer experience, Support Care Cancer source

  • May combine two claims.

    Premisecitation

    First-line bevacizumab plus chemotherapy for ABC yields moderate PFS benefit but no OS benefit.

    “The available data show that bevacizumab combined with ChT as first-line therapy for ABC provides a moderate benefit in progression-free survival (PFS) and no benefit in OS.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [35] Hey, 2020, A systematic review and meta-analysis of bevacizumab in first-line metastatic breast cancer: lessons for research and regulatory enterprises, J Natl Cancer Inst source

  • The quote only partly states this claim.

    Premisecitation

    The ESMO-MCBS v1.1 score for bevacizumab is 2.

    “The ESMO-MCBS v1.1 score for bevacizumab is two.35”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [35] Hey, 2020, A systematic review and meta-analysis of bevacizumab in first-line metastatic breast cancer: lessons for research and regulatory enterprises, J Natl Cancer Inst source

  • May combine two claims.

    Premisecitation

    There is no evidence that sensitive communication of more prognostic information harms patients or raises anxiety or distress.

    “Although some physicians may avoid discussing prognosis for fear of upsetting the patient or destroying hope, there is no evidence that increased information about prognosis with sensitive communication is harmful to patients, or that it increases anxiety or distress.25, 26, 27, 28, 29, 30”
    Quote in the paperSubstantial claim0 of 6 sources checked
    • cites [25] Fallowfield, 2002, Truth may hurt but deceit hurts more: communication in palliative care, Palliat Med source
    • cites [26] Barnett, 2006, Does it hurt to know the worst?–psychological morbidity, information preferences and understanding of prognosis in patients with advanced cancer, Psychooncology source
    • cites [27] Enzinger, 2015, Outcomes of prognostic disclosure: associations with prognostic understanding, distress, and relationship with physician among patients with advanced cancer, J Clin Oncol source
    • cites [28] Gattellari, 2002, When the treatment goal is not cure: are cancer patients equipped to make informed decisions?, J Clin Oncol source
    • cites [29] Hagerty, 2005, Communicating with realism and hope: incurable cancer patients' views on the disclosure of prognosis, J Clin Oncol source
    • cites [30] Smith, 2010, Giving honest information to patients with advanced cancer maintains hope, Oncology (Williston Park)

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Previous ABC recommendations not needing update were not re-voted but were reviewed by all panel members by email and remain valid.

    “Previous ABC recommendations that did not require update or only minor changes were not re-voted but were reviewed by all panel members by e-mail and remain valid.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In pretreated ABC patients, tucatinib plus capecitabine and trastuzumab improved PFS (median 7.8 vs 5.6 months; HR 0.54; 95% CI 0.42-0.71; P<0.001) and OS (median 21.9 vs 17.4 months; HR 0.66; 95% CI 0.50-0.88; P=0.005) versus capecitabine/trastuzumab/placebo.

    “Tucatinib, a highly selective inhibitor of the HER2 tyrosine kinase, used in combination with capecitabine and trastuzumab in a population of ABC patients pretreated with trastuzumab, pertuzumab and trastuzumab emtansine (T-DM1), demonstrated improvement of PFS (median 7.8 months versus 5.6 months, HR 0.54; 95% CI 0.42-0.71, P < 0.001) and OS (median 21.9 months versus 17.4 months, HR 0.66; 95% CI”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [62] Murthy, 2020, Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer, N Engl J Med source

  • May combine two claims.

    Premisecitation

    The NALA study lacked a trastuzumab plus capecitabine comparator arm, which had previously shown superior OS to lapatinib plus capecitabine in first- and second-line settings.

    “Furthermore, the NALA study has a severe limitation of not having a comparator arm with trastuzumab plus capecitabine, which was previously shown to provide superior OS to lapatinib plus capecitabine in the first- and second-line settings.67”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [67] Pivot, 2015, CEREBEL (EGF111438): a phase III, randomized, open-label study of lapatinib plus capecitabine versus trastuzumab plus capecitabine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer, J Clin Oncol source

  • May combine two claims.

    Premisecitation

    Neratinib reduced disease progression risk by 24% (95% CI 0.63-0.93; P=0.006; medians not provided), with marginal PFS difference and no OS impact versus lapatinib (both with capecitabine), at the cost of increased toxicity.

    “Neratinib provided a small reduction in the risk of disease progression of 24% (95% CI 0.63-0.93; P = 0.006, medians not provided), a marginal difference in PFS and no impact on OS (co-primary end point) compared with lapatinib (both in combination with capecitabine), at the cost of increased toxicity.66”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [66] Saura, 2019, Neratinib + capecitabine versus lapatinib + capecitabine in patients with HER2+ metastatic breast cancer previously treated with ≥ 2 HER2-directed regimens: findings from the multinational, randomized, phase III NALA trial, J Clin Oncol source

  • May combine two claims.

    Premisecitation

    Low ER (1%-10%) HER2-negative tumours may share morphological and biological features with triple-negative breast cancer and have similarly poor survival.

    “They may share morphological (high grade, poor differentiation)92 and biological features93 , 94 with TNBC and experience a similarly poor survival.95 , 96”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [92] Gloyeske, 2014, Low ER+ breast cancer: is this a distinct group?, Am J Clin Pathol source
    • cites [93] Deyarmin, 2013, Effect of ASCO/CAP guidelines for determining ER status on molecular subtype, Ann Surg Oncol source
    • cites [94] Iwamoto, 2012, Estrogen receptor (ER) mRNA and ER-related gene expression in breast cancers that are 1% to 10% ER-positive by immunohistochemistry, J Clin Oncol source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Panel members with potential conflicts of interest or insufficient expertise were instructed to abstain from voting.

    “All panel members were instructed to vote on all questions, and any members with a potential conflict of interest or who did not feel comfortable answering the question (e.g. due to lack of expertise in a particular field) were instructed to vote ‘abstain’.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductreasoning

    Side-effect and difficult-symptom statements were not voted at the consensus session but were discussed and unanimously agreed by email, and are considered to have 100% consensus.

    “Statements related to the management of side-effects and difficult symptoms, included under the supportive and palliative care section, were not voted on during the consensus session, but were discussed and unanimously agreed by e-mail, and are therefore considered to have 100% consensus agreement.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Tucatinib combination increased toxicity, mainly grade ≥3 diarrhoea and elevated aminotransferase levels, without frequent treatment discontinuation.

    “This was achieved at the expense of increased toxicity, mostly diarrhoea and elevated aminotransferase levels of grade ≥3, but did not lead to frequent treatment discontinuation.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [62] Murthy, 2020, Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer, N Engl J Med source

  • May combine two claims.

    Premisecitation

    Margetuximab produced only a 0.9-month PFS prolongation (HR 0.76; 95% CI 0.59-0.98; P=0.033) versus trastuzumab (both with physician's choice chemotherapy), no OS benefit, and a good toxicity profile.

    “Margetuximab resulted in only a 0.9-month PFS prolongation (HR 0.76; 95% CI 0.59-0.98, P = 0.033) compared with trastuzumab (both combined with ChT of physician's choice), no OS benefit and a good toxicity profile.65”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [65] Rugo, 2019, SOPHIA primary analysis: a phase 3 (P3) study of margetuximab (M) + chemotherapy (C) versus trastuzumab (T) + C in patients (pts) with HER2+ metastatic (met) breast cancer (MBC) after prior anti-HER2 therapies (Tx), J Clin Oncol source

  • May combine two claims.

    Premisecitation

    Sacituzumab govitecan-hziy showed an overall response rate of 33.3% (95% CI 24.6-43.1) and a median duration of response of 7.7 months (95% CI 4.9-10.8) in a phase I/II study of 108 patients with advanced triple-negative advanced breast cancer.

    “The overall response rate was 33.3% (95% CI 24.6-43.1), with a median duration of response of 7.7 months (95% CI 4.9-10.8).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [72] Bardia, 2019, Sacituzumab govitecan-hziy in refractory metastatic triple-negative breast cancer, N Engl J Med source

  • May combine two claims.

    Premisecitation

    Among responders to sacituzumab govitecan-hziy, 55.6% maintained response for at least 6 months and 16.7% for at least 12 months.

    “Of the patients with a response to sacituzumab govitecan-hziy, 55.6% maintained their response for ≥6 months and 16.7% maintained their response for ≥12 months.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [72] Bardia, 2019, Sacituzumab govitecan-hziy in refractory metastatic triple-negative breast cancer, N Engl J Med source

  • May combine two claims.

    Premisecitation

    Updated IMpassion-130 data showed a progression-free survival difference of 2.5 months and an overall survival difference of 7 months in the PD-L1-positive population.

    “Recently, these data were updated showing a PFS difference of 2.5 months and an OS difference of 7 months in the PD-L1-positive population.69”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [69] Schmid, 2020, Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial, Lancet Oncol source

  • May combine two claims.

    Premisecitation

    Leptomeningeal disease carries a poor prognosis, with a median overall survival of approximately 4 weeks, which can be prolonged to a few months in some patients with aggressive multimodal treatment.

    “LMD carries a poor prognosis, with a median OS of approximately 4 weeks which can be prolonged to a few months in some patients with aggressive multimodal treatment.100”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [100] Franzoi, 2019, Leptomeningeal carcinomatosis in patients with breast cancer, Crit Rev Oncol Hematol source

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    ASCO-CAP guidelines acknowledged that tumours with 1%-10% ER staining represent a new reporting category, noting the lack of data on endocrine therapy benefit and the proximity to ER-negative breast cancer.

    “Recently, the ASCO-College of American Pathologists (CAP) guidelines acknowledged that patients with tumours between 1% and 10% of ER staining represent a new reporting category, stipulating the lack of data concerning benefit from ET and the proximity to ER-negative breast cancer of this patient group.98”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [98] Allison, 2020, Estrogen and progesterone receptor testing in breast cancer: ASCO/CAP Guideline update, J Clin Oncol source

  • May combine two claims.

    Premisecitation

    Decreased or no interest in sexual activity was frequently reported and significantly associated with less satisfaction and more discomfort (dyspareunia) in breast cancer patients.

    “decreased or no interest in sexual activity was frequently reported with a significant association to less satisfaction and more discomfort (dyspareunia)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [124] Mayer, 2019, Sexual activity and quality of life in patients after treatment for breast and ovarian cancer, Arch Gynecol Obstet source

  • May combine two claims.

    Premisecitation

    Lack of sexual desire was not associated with global health status, quality of life or the ability to experience orgasms.

    “however, the lack of desire was not associated with global health status, QoL or the ability to experience orgasms”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [124] Mayer, 2019, Sexual activity and quality of life in patients after treatment for breast and ovarian cancer, Arch Gynecol Obstet source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Several organisations, such as ASCO, have called for measures to ensure adequate protection of cancer patients.

    “Several organisations, such as ASCO,108 have been calling for measures to ensure adequate protection of cancer patients.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [108] Page, 2019, Opioids and cancer pain: patients' needs and access challenges, J Oncol Pract source

  • May combine two claims.

    Premisecitation

    In Europe and worldwide, access to pain control is inadequate and very unequal.

    “Yet, in Europe and all over the world, there is inadequate and very unequal access to pain control,105”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [105] Knaul, 2018, Alleviating the access abyss in palliative care and pain relief—an imperative of universal health coverage: the Lancet Commission report, Lancet source
34 of 34

  • The authors state this as an assumption.

    The ABC 5 guidelines assume accessibility to all available therapies.

    “assuming accessibility to all available therapies”

  • The paper relies on this without support.

    Visceral crisis occurs in about 10-15% of first-line ABC cases.

    “This situation is estimated to occur in only around 10%-15% of first-line ABC cases”

  • The paper relies on this without support.

    No biomarkers currently enable accurate identification of patients who can be treated with endocrine therapy alone.

    “There are currently no biomarkers to enable accurate identification of these patients.”

  • The paper relies on this without support.

    There are no comparative data between the four new anti-HER2 agents (tucatinib, trastuzumab deruxtecan, margetuximab, neratinib).

    “there are no comparative data between these four new anti-HER2 agents”

  • The paper relies on this without support.

    The optimal sequence of treatments after trastuzumab, pertuzumab and T-DM1 is currently unknown.

    “the question regarding the optimal sequence of treatments after trastuzumab, pertuzumab and T-DM1 is currently unknown.”

  • The paper relies on this without support.

    Triple-negative advanced breast cancer is clinically and molecularly not one but many diseases.

    “with the recognition that both clinically and molecularly this is not one but many diseases.”

  • The paper relies on this without support.

    For most patients, chemotherapy remains the only available non-investigational systemic treatment option for non-BRCA-mutated triple-negative advanced breast cancer.

    “For most patients, ChT remains the only available non-investigational systemic treatment option for non-BRCA-mutated triple-negative ABC”

  • The paper relies on this without support.

    At present, only germline mutations in BRCA1/2 have clinical utility and therapeutic impact.

    “However, at present, only germline mutations in BRCA1/2 have any clinical utility and therapeutic impact.”

  • The paper relies on this without support.

    A mutation in another moderate- to high-penetrance gene has limited clinical implications in advanced breast cancer.

    “a mutation in another moderate- to high-penetrance gene has limited clinical implications in the setting of ABC”

  • The paper relies on this without support.

    The majority of PIK3CA mutations affect hot spots in exons 9 and 20.

    “The majority of PIK3CA mutations affect hot spots i.e. the three most frequent in exons 9 and 20”

  • The paper relies on this without support.

    PIK3CA mutations are present in up to 40% of metastatic luminal breast cancer.

    “They are present in up to 40% of metastatic luminal breast cancer.”

  • The paper relies on this without support.

    PIK3CA mutations activate the alpha isoform of PI3K and drive oncogenicity.

    “The mutations activate the alpha isoform of PI3K and drive oncogenicity.”

  • The paper relies on this without support.

    Acquisition of ESR1 mutations is frequent in advanced breast cancer patients previously treated with aromatase inhibitors (20%-40%) and is one mechanism of resistance to hormonal therapies.

    “Acquisition of ESR1 mutations, frequent in ABC patients previously treated by AIs (20%-40%), is one of the mechanisms of resistance to hormonal therapies.”

  • The paper relies on this without support.

    ESR1 mutations cause ligand-independent, constitutive activity of the estrogen receptor.

    “The consequence is a ligand-independent, constitutive activity of ER.”

  • The paper relies on this without support.

    Leptomeningeal disease is a rare complication of breast cancer with a 5% incidence rate.

    “Leptomeningeal disease (LMD) is a rare complication of breast cancer with a 5% incidence rate.”

  • The paper relies on this without support.

    Currently, there is no accepted standard of care for breast cancer leptomeningeal disease.

    “Currently, there is no accepted standard of care for breast cancer LMD and recommendations are essentially expert opinion-based.”

  • The paper relies on this without support.

    Many therapies for advanced breast cancer are associated with estrogen deprivation and patients often suffer from menopausal symptoms.

    “Many therapies for ABC are associated with estrogen deprivation and patients often suffer from menopausal symptoms”

  • The paper relies on this without support.

    Hormone replacement therapy is contraindicated due to the endocrine character of the disease.

    “Hormone replacement therapy is contraindicated due to the endocrine character of the disease”

  • The paper relies on this without support.

    Dyspareunia is often caused by vaginal dryness.

    “Dyspareunia is often caused by vaginal dryness.”

  • The paper relies on this without support.

    At first recurrence, one out of four patients is younger than 50 years old and premenopausal.

    “At first recurrence, one out of four patients is younger than 50 years old and premenopausal.”
20 of 20

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Cites

Flagged first, then by citations

5 of the 147 references couldn’t be matched to a known paper.

Research works printed but not linked: 3

  1. Tripathy, 2018, Cancer Res, 78
  2. Juric, 2020, Cancer Res, 80
  3. 2019, Cannabis and cannabinoids, Med Lett Drugs Ther, 61, 179

Cited by

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Authors
Cardoso, F., Paluch-Shimon, S., Senkus, E., Curigliano, G., Aapro, M. S., André, F., Barrios, C. H., Bergh, J., Bhattacharyya, G. S., Biganzoli, L., Boyle, F., Cardoso, M.-J., Carey, L. A., Cortés, J., El Saghir, N. S., Elzayat, M., Eniu, A., Fallowfield, L., Francis, P. A., Gelmon, K., Gligorov, J., Haidinger, R., Harbeck, N., Hu, X., Kaufman, B., Kaur, R., Kiely, B. E., Kim, S.-B., Lin, N. U., Mertz, S. A., Neciosup, S., Offersen, B. V., Ohno, S., Pagani, O., Prat, A., Penault-Llorca, F., Rugo, H. S., Sledge, G. W., Thomssen, C., Vorobiof, D. A., Wiseman, T., Xu, B., Norton, L., Costa, A., & Winer, E. P.
Affiliations
  • Champalimaud Foundation (PT)
  • Gdańsk Medical University (PL)
  • University of Milan (IT)
  • Clinique de Genolier (CH)
  • Institut Gustave Roussy (FR)
  • Latin American Cooperative Oncology Group (LACOG) (BR)
  • Karolinska University Hospital (SE)
  • Ospedale di Prato Santo Stefano (IT)
  • Royal North Shore Hospital (AU)
  • University of North Carolina at Chapel Hill (US)
  • Vall d'Hebron Institute of Oncology (ES)
  • Europa Donna (IT)
  • Hôpital Riviera-Chablais (CH)
  • Brighton and Sussex Medical School (GB)
  • Peter MacCallum Cancer Centre (AU)
  • BC Cancer Agency (CA)
  • Sorbonne Université (FR)
  • Ludwig-Maximilians-Universität München (DE)
  • Fudan University (CN)
  • Sheba Medical Center (IL)
  • National Health and Medical Research Council (AU)
  • Asan Medical Center (KR)
  • Dana-Farber Cancer Institute (US)
  • Metastatic Breast Cancer Network (US)
  • Instituto Nacional de Enfermedades Neoplásicas (PE)
  • Aarhus University Hospital (DK)
  • The Cancer Institute Hospital (JP)
  • University Hospital of Geneva (CH)
  • Hospital Clínic de Barcelona (ES)
  • Inserm (FR)
  • University of California, San Francisco (US)
  • Stanford Medicine (US)
  • Martin Luther University Halle-Wittenberg (DE)
  • Royal Marsden NHS Foundation Trust (GB)
  • Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
  • Memorial Sloan Kettering Cancer Center (US)
  • European School of Oncology (CH)
Corresponding author
Cardoso, F.
ORCID
Venue
Annals of Oncology
Publisher
Elsevier BV
Published
2020-12
Volume
31
Issue
12
Pages
1623-1649
ISSN
0923-7534 (ISSN-L)
DOI
10.1016/j.annonc.2020.09.010
PMC
PMC7510449
OpenAlex
W4206666777
Cited by
1,369
References
147
Citations by year
2026: 151 · 2025: 182 · 2024: 238 · 2023: 276 · 2022: 293 · 2021: 210 · 2020: 18
FWCI
68.55
Type
journal article
Language
en
Open access
Licence
Locations
  • Annals of Oncology (publishedVersion)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, other-oa)
  • Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (submittedVersion)
  • HAL (submittedVersion)
  • Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
  • Minerva Access (University of Melbourne) (submittedVersion)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by)
  • The Sydney eScholarship Repository (The University of Sydney) (submittedVersion)
Funders
ESMO
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Advanced Breast Cancer Therapies
  • Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
Keywords
advanced breast cancer, metastatic breast cancer, locally advanced breast cancer, treatment guidelines, HER2-positive breast cancer, breast cancer subtypes, overall survival

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read under definition version 3 (extract-v3) on 2026-09-28.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-09-28.

Cited sources are checked by gpt-6-sol.

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