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ASCO Rapid Recommendation Updates highlight revisions to select ASCO guideline recommendations as a response to the emergence of new and practice-changing data. The rapid updates are supported by an evidence review and follow the guideline development processes outlined in the ASCO Guideline Methodology Manual. The goal of these articles is to disseminate updated recommendations, in a timely manner, to better inform health practitioners and the public on the best available cancer care options. Guidelines and updates are not intended to substitute for independent professional judgment of the treating provider and do not account for individual variation among patients. See appendix for disclaimers and other important information (Appendix 1 and Appendix 2, online only) .

ASCO Rapid Recommendation Updates highlight revisions to select ASCO guideline recommendations as a response to the emergence of new and practice-changing data. The rapid updates are supported by an evidence review and follow the guideline development processes outlined in the ASCO Guideline Methodology Manual. The goal of these articles is to disseminate updated recommendations, in a timely manner, to better inform health practitioners and the public on the best available cancer care options. Guidelines and updates are not intended to substitute for independent professional judgment of the treating provider and do not account for individual variation among patients. See appendix for disclaimers and other important information (Appendix 1 and Appendix 2, online only) .

Purpose: To develop recommendations for germline mutation testing for patients with breast cancer., Methods: An ASCO-Society of Surgical Oncology (SSO) panel convened to develop recommendations based on a systematic review and formal consensus process., Results: Forty-seven articles met eligibility criteria for the germline mutation testing recommendations; 18 for the genetic counseling recommendations., Recommendations: BRCA1 / 2 mutation testing should be offered to all newly diagnosed patients with breast cancer ≤65 years and select patients >65 years based on personal history, family history, ancestry, or eligibility for poly(ADP-ribose) polymerase (PARP) inhibitor therapy. All patients with recurrent breast cancer who are candidates for PARP inhibitor therapy should be offered BRCA1 / 2 testing, regardless of family history. BRCA1 / 2 testing should be offered to women who develop a second primary cancer in the ipsilateral or contralateral breast. For patients with prior history of breast cancer and without active disease, testing should be offered to patients diagnosed ≤65 years and selectively in patients diagnosed after 65 years, if it will inform personal and family risk. Testing for high-penetrance cancer susceptibility genes beyond BRCA1 / 2 should be offered to those with supportive family histories; testing for moderate-penetrance genes may be offered if necessary to inform personal and family cancer risk. Patients should be provided enough pretest information for informed consent; those with pathogenic variants should receive individualized post-test counseling. Variants of uncertain significance should not impact management, and patients with such variants should be followed for reclassification. Referral to providers experienced in clinical cancer genetics may help facilitate patient selection and interpretation of expanded testing, and provide counseling of individuals without pathogenic germline variants but with significant family history.Additional information is available at www.asco.org/breast-cancer-guidelines.

Purpose: To update the ASCO guideline (2018) on the practical assessment and management of age-associated vulnerabilities in older patients undergoing systemic cancer therapy., Methods: An Expert Panel conducted a systematic review to identify relevant randomized clinical trials (RCTs), systematic reviews, and meta-analyses from January 2016 to December 2022., Results: A total of 26 publications met eligibility criteria and form the evidentiary basis for the update., Recommendations: The Expert Panel reiterates its overarching recommendation from the prior guideline that geriatric assessment (GA), including all essential domains, should be used to identify vulnerabilities or impairments that are not routinely captured in oncology assessments for all patients over 65 years old with cancer. Based on recently published RCTs demonstrating significantly improved clinical outcomes, all older adults with cancer (65+ years old) receiving systemic therapy with GA-identified deficits should have GA-guided management (GAM) included in their care plan. GAM includes using GA findings to inform cancer treatment decision-making as well as to address impairments through appropriate interventions, counseling, and/or referrals. A GA should include high priority aging-related domains known to be associated with outcomes in older adults with cancer: physical and cognitive function, emotional health, comorbid conditions, polypharmacy, nutrition, and social support. Clinical adaptation of the GA based on patient population, resources, and time is appropriate.The Panel recommends the Practical Geriatric Assessment as one option for this purpose (https://old-prod.asco.org/sites/new-www.asco.org/files/content-files/practice-patients/documents/2023-PGA-Final.pdf; https://youtu.be/jnaQIjOz2Dw; https://youtu.be/nZXtwaGh0Z0).Additional information is available at www.asco.org/supportive-care-guidelines.

Purpose.—: To update the American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast cancer. An Update Panel is aware that a new generation of antibody-drug conjugates targeting the HER2 protein is active against breast cancers that lack protein overexpression or gene amplification., Methods.—: The Update Panel conducted a systematic literature review to identify signals for updating recommendations., Results.—: The search identified 173 abstracts. Of 5 potential publications reviewed, none constituted a signal for revising existing recommendations., Recommendations.—: The 2018 ASCO-CAP recommendations for HER2 testing are affirmed., Discussion.—: HER2 testing guidelines have focused on identifying HER2 protein overexpression or gene amplification in breast cancer to identify patients for therapies that disrupt HER2 signaling. This update acknowledges a new indication for trastuzumab deruxtecan when HER2 is not overexpressed or amplified but is immunohistochemistry (IHC) 1+ or 2+ without amplification by in situ hybridization. Clinical trial data on tumors that tested IHC 0 are limited (excluded from DESTINY-Breast04), and evidence is lacking that these cancers behave differently or do not respond similarly to newer HER2 antibody-drug conjugates. Although current data do not support a new IHC 0 versus 1+ prognostic or predictive threshold for response to trastuzumab deruxtecan, this threshold is now relevant because of the trial entry criteria that supported its new regulatory approval. Therefore, although it is premature to create new result categories of HER2 expression (eg, HER2-Low, HER2-Ultra-Low), best practices to distinguish IHC 0 from 1+ are now clinically relevant. This update affirms prior HER2 reporting recommendations and offers a new HER2 testing reporting comment to highlight the current relevance of IHC 0 versus 1+ results and best practice recommendations to distinguish these often subtle differences. Additional information is available at www.asco.org/breast-cancer-guidelines., Competing Interests: Authors’ disclosures of potential conflicts of interest are shown after the references., (Copyright 2023 College of American Pathologists and the American Society of Clinical Oncology. This guideline update was developed through collaboration among the College of American Pathologists and the American Society of Clinical Oncology and has been jointly published by invitation and consent in the Archives of Pathology & Laboratory Medicine and the Journal of Clinical Oncology. It has been edited in accordance with style standards established at the Journal of Clinical Oncology. All rights reserved.)

Purpose: To update ASCO-College of American Pathologists (CAP) recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast cancer. The Panel is aware that a new generation of antibody-drug conjugates (ADCs) targeting the HER2 protein is active against breast cancers that lack protein overexpression or gene amplification., Methods: An Update Panel conducted a systematic literature review to identify signals for updating recommendations., Results: The search identified 173 abstracts. Of five potential publications reviewed, none constituted a signal for revising existing recommendations., Recommendations: The 2018 ASCO-CAP recommendations for HER2 testing are affirmed., Discussion: HER2 testing guidelines have focused on identifying HER2 protein overexpression or gene amplification in breast cancer to identify patients for therapies that disrupt HER2 signaling. This update acknowledges a new indication for trastuzumab deruxtecan when HER2 is not overexpressed or amplified but is immunohistochemistry (IHC) 1+ or 2+ without amplification by in situ hybridization. Clinical trial data on tumors that tested IHC 0 are limited (excluded from DESTINY-Breast04), and evidence is lacking that these cancers behave differently or do not respond similarly to newer HER2 ADCs. Although current data do not support a new IHC 0 versus 1+ prognostic or predictive threshold for response to trastuzumab deruxtecan, this threshold is now relevant because of the trial entry criteria that supported its new regulatory approval. Therefore, while it is premature to create new result categories of HER2 expression (eg, HER2-Low, HER2-Ultra-Low), best practices to distinguish IHC 0 from 1+ are now clinically relevant. This Update affirms prior HER2 reporting recommendations and offers a new HER2 testing reporting comment to highlight the current relevance of IHC 0 versus 1+ results and best practice recommendations to distinguish these often subtle differences.Additional information is available at www.asco.org/breast-cancer-guidelines.

ASCO Rapid Recommendations Updates highlight revisions to select ASCO guideline recommendations as a response to the emergence of new and practice-changing data. The rapid updates are supported by an evidence review and follow the guideline development processes outlined in the ASCO Guideline Methodology Manual. The goal of these articles is to disseminate updated recommendations, in a timely manner, to better inform health practitioners and the public on the best available cancer care options. See the Appendix for disclaimers and other important information ( Appendix 1 and Appendix 2 , online only) .

Purpose: To update the ASCO Biomarkers to Guide Systemic Therapy for Metastatic Breast Cancer (MBC) guideline., Methods: An Expert Panel conducted a systematic review to identify randomized clinical trials and prospective-retrospective studies from January 2015 to January 2022., Results: The search identified 19 studies informing the evidence base., Recommendations: Candidates for a regimen with a phosphatidylinositol 3-kinase inhibitor and hormonal therapy should undergo testing for PIK3CA mutations using next-generation sequencing of tumor tissue or circulating tumor DNA (ctDNA) in plasma to determine eligibility for alpelisib plus fulvestrant. If no mutation is found in ctDNA, testing in tumor tissue, if available, should be used. Patients who are candidates for poly (ADP-ribose) polymerase (PARP) inhibitor therapy should undergo testing for germline BRCA1 and BRCA2 pathogenic or likely pathogenic mutations to determine eligibility for a PARP inhibitor. There is insufficient evidence for or against testing for a germline PALB2 pathogenic variant to determine eligibility for PARP inhibitor therapy in the metastatic setting. Candidates for immune checkpoint inhibitor therapy should undergo testing for expression of programmed cell death ligand-1 in the tumor and immune cells to determine eligibility for treatment with pembrolizumab plus chemotherapy. Candidates for an immune checkpoint inhibitor should also undergo testing for deficient mismatch repair/microsatellite instability-high to determine eligibility for dostarlimab-gxly or pembrolizumab, as well as testing for tumor mutational burden. Clinicians may test for NTRK fusions to determine eligibility for TRK inhibitors. There are insufficient data to recommend routine testing of tumors for ESR1 mutations, for homologous recombination deficiency, or for TROP2 expression to guide MBC therapy selection. There are insufficient data to recommend routine use of ctDNA or circulating tumor cells to monitor response to therapy among patients with MBC.Additional information can be found at www.asco.org/breast-cancer-guidelines.

Competing Interests: Nadine M. TungResearch Funding: AstraZeneca (Inst)No other potential conflicts of interest were reported.

ASCO Rapid Recommendations Updates highlight revisions to select ASCO guideline recommendations as a response to the emergence of new and practice-changing data. The rapid updates are supported by an evidence review and follow the guideline development processes outlined in the ASCO Guideline Methodology Manual. The goal of these articles is to disseminate updated recommendations, in a timely manner, to better inform health practitioners and the public on the best available cancer care options., Competing Interests: Dawn L. HershmanConsulting or Advisory Role: AIM Specialty HealthNo other potential conflicts of interest were reported.

Purpose: To update recommendations of the American Society of Clinical Oncology (ASCO)-Ontario Health (Cancer Care Ontario [CCO]) adjuvant bone-modifying agents in breast cancer guideline., Methods: An Expert Panel conducted a systematic review to identify new, potentially practice-changing data., Results: Four articles met eligibility criteria and form the evidentiary basis for revision of the previous recommendations., Recommendations: Adjuvant bisphosphonate therapy should be discussed with all postmenopausal patients (natural or therapy-induced) with primary breast cancer, irrespective of hormone receptor status and human epidermal growth factor receptor 2 status, who are candidates to receive adjuvant systemic therapy. Adjuvant bisphosphonates, if used, are not substitutes for standard anticancer modalities. The benefit of adjuvant bisphosphonate therapy will vary depending on the underlying risk of recurrence and is associated with a modest improvement in overall survival. The NHS PREDICT tool provides estimates of the benefit of adjuvant bisphosphonate therapy and may aid in decision making. Factors influencing the decision to recommend adjuvant bisphosphonate use should include patients' risk of recurrence, risk of side effects, financial toxicity, drug availability, patient preferences, comorbidities, and life expectancy. When an adjuvant bisphosphonate is used to prevent breast cancer recurrence, the therapeutic options recommended by the Panel include oral clodronate, oral ibandronate, and intravenous zoledronic acid. The Panel supports starting bisphosphonate therapy early, consistent with the points outlined in the parent CCO-ASCO guideline; this is a consensus recommendation. The Panel does not recommend adjuvant denosumab to prevent breast cancer recurrence, because studies did not show a consistent reduction of breast cancer recurrence in any subset of those with early-stage breast cancer.Additional information can be found at www.asco.org/breast-cancer-guideline., Competing Interests: Andrea EisenOther Relationship: Cancer Care Ontario Melissa K. AccordinoHonoraria: Sermo (I), M3 (I), Charter Oak Research, ExpertConnect, Medscape, Deerfield Management, Incrowd, Massive BioOther Relationship: Onclive Mark J. ClemonsHonoraria: PfizerConsulting or Advisory Role: Cornerstone Research Group, ApotexTravel, Accommodations, Expenses: Pfizer Sukhbinder Dhesy-ThindHonoraria: PfizerConsulting or Advisory Role: Novartis Canada Pharmaceuticals Inc, Seattle Genetics Melissa S. DillmonStock and Other Ownership Interests: Johnson & Johnson (I), Bristol Myers Squibb (I)Consulting or Advisory Role: Puma Biotechnology Elizabeth S. FrankHonoraria: AstraZenecaTravel, Accommodations, Expenses: Roche Sigrun HallmeyerLeadership: Association of Community Cancer Centers (ACCC)Honoraria: Cardinal HealthConsulting or Advisory Role: Bristol Myers Squibb, Cardinal Health, Array PharamceuticalSpeakers' Bureau: Bristol Myers SquibbTravel, Accommodations, Expenses: Cardinal Health, Bristol Mers SquibbUncompensated Relationships: Society for Immunotherapy of Cancer Beverly MoyConsulting or Advisory Role: MOTUS (I)Research Funding: Puma Biotechnology (Inst) Alia ThawerHonoraria: Knight Pharmaceuticals, Novartis Canada Pharmaceuticals Inc, Pfizer, GlaxoSmithKline Canada, AbbVie, AstraZeneca CanadaConsulting or Advisory Role: Ipsen, Amgen, Novartis, Lilly, Sandoz-Novartis, Pfizer, EisaiResearch Funding: Novartis, AstraZeneca Joy Y. WuResearch Funding: Radius Health Catherine H. Van PoznakResearch Funding: Bayer (Inst)Patents, Royalties, Other Intellectual Property: UpToDateNo other potential conflicts of interest were reported.

ASCO Rapid Recommendations Updates highlight revisions to select ASCO guideline recommendations as a response to the emergence of new and practice-changing data. The rapid updates are supported by an evidence review and follow the guideline development processes outlined in the ASCO Guideline Methodology Manual. The goal of these articles is to disseminate updated recommendations, in a timely manner, to better inform health practitioners and the public on the best available cancer care options., Competing Interests: Rachel A. FreedmanEmployment: Firefly HealthStock and Other Ownership Interests: Firefly HealthResearch Funding: Puma Biotechnology (Inst), Eisai (Inst), Genentech/Roche (Inst)No other potential conflicts of interest were reported.

Purpose: To update recommendations of the ASCO systemic therapy for hormone receptor (HR)-positive metastatic breast cancer (MBC) guideline., Methods: An Expert Panel conducted a systematic review to identify new, potentially practice-changing data., Results: Fifty-one articles met eligibility criteria and form the evidentiary basis for the recommendations., Recommendations: Alpelisib in combination with endocrine therapy (ET) should be offered to postmenopausal patients, and to male patients, with HR-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA -mutated, ABC, or MBC following prior endocrine therapy with or without a cyclin-dependent kinase (CDK) 4/6 inhibitor. Clinicians should use next-generation sequencing in tumor tissue or cell-free DNA in plasma to detect PIK3CA mutations. If no mutation is found in cell-free DNA, testing in tumor tissue, if available, should be used as this will detect a small number of additional patients with PIK3CA mutations. There are insufficient data at present to recommend routine testing for ESR1 mutations to guide therapy for HR-positive, HER2-negative MBC. For BRCA1 or BRCA2 mutation carriers with metastatic HER2-negative breast cancer, olaparib or talazoparib should be offered in the 1st-line through 3rd-line setting. A nonsteroidal aromatase inhibitor (AI) and a CDK4/6 inhibitor should be offered to postmenopausal women with treatment-naïve HR-positive MBC. Fulvestrant and a CDK4/6 inhibitor should be offered to patients with progressive disease during treatment with AIs (or who develop a recurrence within 1 year of adjuvant AI therapy) with or without one line of prior chemotherapy for metastatic disease, or as first-line therapy. Treatment should be limited to those without prior exposure to CDK4/6 inhibitors in the metastatic setting.Additional information can be found at www.asco.org/breast-cancer-guidelines., Competing Interests: Reprint Requests: 2318 Mill Road, Suite 800, Alexandria, VA 22314; guidelines@asco.org Debra L. BartonResearch Funding: Merck Lesley J. FallowfieldHonoraria: Voluntis, Genomic Health, NanoString Technologies, Novartis, Pfizer, MSD, Novartis, AbbVie, Clovis OncologyConsulting or Advisory Role: Puma Biotechnology, Voluntis, AstraZeneca, Takeda, Genomic Health/Exact Sciences, Lilly, Seagen, RocheResearch Funding: Bristol Myers Squibb, Novartis, LillyTravel, Accommodations, Expenses: Genomic Health Stephen R. D. JohnstonHonoraria: Pfizer, Novartis, Eisai, AstraZeneca, Roche, LillyConsulting or Advisory Role: Lilly, Puma Biotechnology, Novartis, PfizerResearch Funding: Pfizer, Puma BiotechnologyExpert Testimony: Novartis Jennifer K. LittonHonoraria: UpToDateConsulting or Advisory Role: Pfizer, AstraZeneca, Medivation/Pfizer, Ayala PharmaceuticalsSpeakers' Bureau: Physicans' Education Resource, UpToDate, Med Learning Group, Medscape, Prime Oncology, Clinical Care Options, MedpageResearch Funding: Genentech, Pfizer, EMD Serono, AstraZeneca, Zenith Epigenetics, MerckPatents, Royalties, Other Intellectual Property: UptoDateTravel, Accommodations, Expenses: Physicans' Education Resource, Med Learning Group, Medscape, Clinical Care OptionsOther Relationship: Medivation/Pfizer Praveen VikasStock and Other Ownership Interests: Moderna Therapeutics, NovavaxResearch Funding: Sanofi Rachel L. YungResearch Funding: Novartis, Odonate Therapeutics, American Cancer Society/Pfizer Hope S. RugoHonoraria: Puma Biotechnology, MylanConsulting or Advisory Role: SamsungResearch Funding: Macrogenics, OBI Pharma, Eisai, Pfizer, Novartis, Lilly, Genentech, Merck, Immunomedics, Odonate Therapeutics, Daiichi Sankyo, Seattle Genetics, Sermonix Pharmaceuticals, AstraZenecaTravel, Accommodations, Expenses: Pfizer, Novartis, Macrogenics, Mylan, Daiichi Sankyo, AstraZeneca Spain, MerckOpen Payments Link: https://openpaymentsdata.cms.gov/summaryNo other potential conflicts of interest were reported.

ASCO Rapid Recommendations Updates highlight revisions to select ASCO guideline recommendations as a response to the emergence of new and practice-changing data. The rapid updates are supported by an evidence review and follow the guideline development processes outlined in the ASCO Guideline Methodology Manual. The goal of these articles is to disseminate updated recommendations, in a timely manner, to better inform health practitioners and the public on the best available cancer care options., Competing Interests: Nadine M. TungResearch Funding: AstraZenecaNo other potential conflicts of interest were reported.

Purpose: To develop guideline recommendations concerning optimal neoadjuvant therapy for breast cancer., Methods: ASCO convened an Expert Panel to conduct a systematic review of the literature on neoadjuvant therapy for breast cancer and provide recommended care options., Results: A total of 41 articles met eligibility criteria and form the evidentiary basis for the guideline recommendations., Recommendations: Patients undergoing neoadjuvant therapy should be managed by a multidisciplinary care team. Appropriate candidates for neoadjuvant therapy include patients with inflammatory breast cancer and those in whom residual disease may prompt a change in therapy. Neoadjuvant therapy can also be used to reduce the extent of local therapy or reduce delays in initiating therapy. Although tumor histology, grade, stage, and estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2) expression should routinely be used to guide clinical decisions, there is insufficient evidence to support the use of other markers or genomic profiles. Patients with triple-negative breast cancer (TNBC) who have clinically node-positive and/or at least T1c disease should be offered an anthracycline- and taxane-containing regimen; those with cT1a or cT1bN0 TNBC should not routinely be offered neoadjuvant therapy. Carboplatin may be offered to patients with TNBC to increase pathologic complete response. There is currently insufficient evidence to support adding immune checkpoint inhibitors to standard chemotherapy. In patients with hormone receptor (HR)-positive (HR-positive), HER2-negative tumors, neoadjuvant chemotherapy can be used when a treatment decision can be made without surgical information. Among postmenopausal patients with HR-positive, HER2-negative disease, hormone therapy can be used to downstage disease. Patients with node-positive or high-risk node-negative, HER2-positive disease should be offered neoadjuvant therapy in combination with anti-HER2-positive therapy. Patients with T1aN0 and T1bN0, HER2-positive disease should not be routinely offered neoadjuvant therapy.Additional information is available at www.asco.org/breast-cancer-guidelines., Competing Interests: Reprint Requests: 2318 Mill Road, Suite 800, Alexandria, VA 22314; guidelines@asco.org Lisa A. CareyResearch Funding: Innocrin Pharma, Syndax, Immunomedics, Novartis, NanoString Technologies, AbbVie, Seattle GeneticsPatents, Royalties, Other Intellectual Property: Royalty-sharing agreement, investorship interest in licensed IP to startup company, Falcon Therapeutics, that is designing neural stem cell-based therapy for glioblastoma multiforme(OPTIONAL) Uncompensated Relationships: Sanofi, Novartis, G1 Therapeutics, Genentech/Roche, GlaxoSmithKline, Exact Sciences, AstraZeneca/Daiichi Sanyo, Aptitude Health(OPTIONAL) Open Payments Link: https://openpaymentsdata.cms.gov/physician/179671 Neelima DenduluriResearch Funding: Amgen, Novartis, Genentech, Lilly, Pfizer, Daiichi Sankyo, ImmunomedicsTravel, Accommodations, Expenses: Seattle Genetics Sibylle LoiblHonoraria: Chugai PharmaConsulting or Advisory Role: Pfizer, Roche, Novartis, Seattle Genetics, Celgene, Lilly, AstraZeneca/MedImmune, Bristol-Myers Squibb, Merck KGaA, AbbVie, Amgen, prime/Medscape, Daiichi Sankyo, Samsung, Puma Biotechnology, Pierre Fabre, Immunomedics, GlaxoSmithKline, EirGenix, BayerResearch Funding: AbbVie, AstraZeneca, Vifor Pharma, Amgen, Celgene, Novartis, Pfizer, Roche, Cepheid, Myriad Genetics, Immunomedics, Seattle Genetics, Daiichi Sankyo, Pierre FabrePatents, Royalties, Other Intellectual Property: Patent Pending EP14153692.0 Elizabeth A. MorrisResearch Funding: GRAIL Alejandra PerezResearch Funding: Genentech/Roche, Macrogenics, Nektar, Immunomedics, AstraZeneca Meredith M. ReganHonoraria: Bristol-Myers SquibbConsulting or Advisory Role: Ipsen, Tolmar, Bristol-Myers SquibbResearch Funding: Veridex, OncoGenex, Pfizer, Ipsen, Novartis, Merck, Ferring, Celgene, AstraZeneca, Pierre Fabre, Ipsen, Bayer, Bristol-Myers Squibb, Roche, Astellas Pharma, Medivation, Janssen, Millennium Pharamceuticals, Sanofi, Sotio, Dendreon, Pfizer, TerSeraTravel, Accommodations, Expenses: Bristol-Myers Squibb Patricia A. SpearsConsulting or Advisory Role: Pfizer Preeti K. SudheendraHonoraria: Boston ScientificConsulting or Advisory Role: Boston Scientific, Vesper Medical, Sirtex MedicalSpeakers' Bureau: Boston Scientific W. Fraser SymmansStock and Other Ownership Interests: ISIS Pharmaceuticals, Nuvera Biosciences, Delphi Diagnostics, Eiger BioPharmaceuticalsConsulting or Advisory Role: Merck, Almac DiagnosticsPatents, Royalties, Other Intellectual Property: Intellectual propertyTravel, Accommodations, Expenses: Luminex, Merck(OPTIONAL) Uncompensated Relationships: Delphi Diagnostics Rachel L. YungResearch Funding: Novartis, Odonate Therapeutics Dawn L. HershmanConsulting or Advisory Role: AIM Specialty HealthNo other potential conflicts of interest were reported.

Purpose: The aim of this work is to update key recommendations of the ASCO guideline adaptation of the Cancer Care Ontario guideline on the selection of optimal adjuvant chemotherapy regimens for early breast cancer and adjuvant targeted therapy for breast cancer., Methods: An Expert Panel conducted a targeted systematic literature review guided by a signals approach to identify new, potentially practice-changing data that might translate into revised guideline recommendations., Results: The Expert Panel reviewed abstracts from the literature review and identified one article for inclusion that reported results of the phase III, open-label KATHERINE trial. In the KATHERINE trial, patients with stage I to III human epidermal growth factor receptor 2 (HER2)-positive breast cancer with residual invasive disease in the breast or axilla after completing neoadjuvant chemotherapy and HER2-targeted therapy were allocated to adjuvant trastuzumab emtansine (T-DM1; n = 743) or to trastuzumab (n = 743). Invasive disease-free survival was significantly higher in the T-DM1 group than in the trastuzumab arm (hazard ratio, 0.50; 95% CI, 0.39 to 0.64; P < .001), and risk of distant recurrence was lower in patients who received T-DM1 than in patients who received trastuzumab (hazard ratio, 0.60; 95% CI, 0.45 to 0.79). Grade 3 or higher adverse events occurred in 190 patients (25.7%) who received T-DM1 and in 111 patients (15.4%) who received trastuzumab., Recommendations: Patients with HER2-positive breast cancer with pathologic invasive residual disease at surgery after standard preoperative chemotherapy and HER2-targeted therapy should be offered 14 cycles of adjuvant T-DM1, unless there is disease recurrence or unmanageable toxicity. Clinicians may offer any of the available and approved formulations of trastuzumab, including trastuzumab, trastuzumab and hyaluronidase-oysk, and available biosimilars.Additional information can be found at www.asco.org/breast-cancer-guidelines.

Purpose: This Provisional Clinical Opinion update presents a clinically pragmatic approach to hepatitis B virus (HBV) screening and management., Provisional Clinical Opinion: All patients anticipating systemic anticancer therapy should be tested for HBV by 3 tests-hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc) total immunoglobulin (Ig) or IgG, and antibody to hepatitis B surface antigen-but anticancer therapy should not be delayed. Findings of chronic HBV (HBsAg-positive) or past HBV (HBsAg-negative and anti-HBc-positive) infection require HBV reactivation risk assessment.Patients with chronic HBV receiving any systemic anticancer therapy should receive antiviral prophylactic therapy through and for minimum 12 months following anticancer therapy. Hormonal therapy alone should not pose a substantial risk of HBV reactivation in patients with chronic HBV receiving hormonal therapy alone; these patients may follow noncancer HBV monitoring and treatment guidance. Coordination of care with a clinician experienced in HBV management is recommended for patients with chronic HBV to determine HBV monitoring and long-term antiviral therapy after completion of anticancer therapy.Patients with past HBV infection undergoing anticancer therapies associated with a high risk of HBV reactivation, such as anti-CD20 monoclonal antibodies or stem-cell transplantation, should receive antiviral prophylaxis during and for minimum 12 months after anticancer therapy completion, with individualized management thereafter. Careful monitoring may be an alternative if patients and providers can adhere to frequent, consistent follow-up so antiviral therapy may begin at the earliest sign of reactivation. Patients with past HBV undergoing other systemic anticancer therapies not clearly associated with a high risk of HBV reactivation should be monitored with HBsAg and alanine aminotransferase during cancer treatment; antiviral therapy should commence if HBV reactivation occurs.Additional information is available at www.asco.org/supportive-care-guidelines.

Purpose: To develop recommendations for management of patients with breast cancer (BC) with germline mutations in BC susceptibility genes., Methods: The American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology convened an Expert Panel to develop recommendations based on a systematic review of the literature and a formal consensus process., Results: Fifty-eight articles met eligibility criteria and formed the evidentiary basis for the local therapy recommendations; six randomized controlled trials of systemic therapy met eligibility criteria., Recommendations: Patients with newly diagnosed BC and BRCA1 / 2 mutations may be considered for breast-conserving therapy (BCT), with local control of the index cancer similar to that of noncarriers. The significant risk of a contralateral BC (CBC), especially in young women, and the higher risk of new cancers in the ipsilateral breast warrant discussion of bilateral mastectomy. Patients with mutations in moderate-risk genes should be offered BCT. For women with mutations in BRCA1 / 2 or moderate-penetrance genes who are eligible for mastectomy, nipple-sparing mastectomy is a reasonable approach. There is no evidence of increased toxicity or CBC events from radiation exposure in BRCA1 / 2 carriers. Radiation therapy should not be withheld in ATM carriers. For patients with germline TP53 mutations, mastectomy is advised; radiation therapy is contraindicated except in those with significant risk of locoregional recurrence. Platinum agents are recommended versus taxanes to treat advanced BC in BRCA carriers. In the adjuvant/neoadjuvant setting, data do not support the routine addition of platinum to anthracycline- and taxane-based chemotherapy. Poly (ADP-ribose) polymerase (PARP) inhibitors (olaparib and talazoparib) are preferable to nonplatinum single-agent chemotherapy for treatment of advanced BC in BRCA1 / 2 carriers. Data are insufficient to recommend PARP inhibitor use in the early setting or in moderate-penetrance carriers. Additional information available at www.asco.org/breast-cancer-guidelines.

Purpose: To develop recommendations concerning the management of male breast cancer., Methods: ASCO convened an Expert Panel to develop recommendations based on a systematic review and a formal consensus process., Results: Twenty-six descriptive reports or observational studies met eligibility criteria and formed the evidentiary basis for the recommendations., Recommendations: Many of the management approaches used for men with breast cancer are like those used for women. Men with hormone receptor-positive breast cancer who are candidates for adjuvant endocrine therapy should be offered tamoxifen for an initial duration of five years; those with a contraindication to tamoxifen may be offered a gonadotropin-releasing hormone agonist/antagonist plus aromatase inhibitor. Men who have completed five years of tamoxifen, have tolerated therapy, and still have a high risk of recurrence may be offered an additional five years of therapy. Men with early-stage disease should not be treated with bone-modifying agents to prevent recurrence, but could still receive these agents to prevent or treat osteoporosis. Men with advanced or metastatic disease should be offered endocrine therapy as first-line therapy, except in cases of visceral crisis or rapidly progressive disease. Targeted systemic therapy may be used to treat advanced or metastatic cancer using the same indications and combinations offered to women. Ipsilateral annual mammogram should be offered to men with a history of breast cancer treated with lumpectomy regardless of genetic predisposition; contralateral annual mammogram may be offered to men with a history of breast cancer and a genetic predisposing mutation. Breast magnetic resonance imaging is not recommended routinely. Genetic counseling and germline genetic testing of cancer predisposition genes should be offered to all men with breast cancer.

Purpose: To update the ASCO guideline on pharmacologic interventions for breast cancer risk reduction and provide guidance on clinical issues that arise when deciding to use endocrine therapy for breast cancer risk reduction., Methods: An Expert Panel conducted targeted systematic literature reviews to identify new studies., Results: A randomized clinical trial that evaluated the use of anastrozole for reduction of estrogen receptor-positive breast cancers in postmenopausal women at increased risk of developing breast cancer provided the predominant basis for the update., Updated Recommendations: In postmenopausal women at increased risk, the choice of endocrine therapy now includes anastrozole (1 mg/day) in addition to exemestane (25 mg/day), raloxifene (60 mg/day), or tamoxifen (20 mg/day). The decision regarding choice of endocrine therapy should take into consideration age, baseline comorbidities, and adverse effect profiles. Clinicians should not prescribe anastrozole, exemestane, or raloxifene for breast cancer risk reduction to premenopausal women. Tamoxifen 20 mg/day for 5 years is still considered standard of care for risk reduction in premenopausal women who are at least 35 years old and have completed childbearing. Data on low-dose tamoxifen as an alternative to the standard dose for both pre- and postmenopausal women with intraepithelial neoplasia are discussed in the Clinical Considerations section of this article. Additional information is available at www.asco.org/breast-cancer-guidelines.

Purpose: To update the American Society of Clinical Oncology endorsement of the Cancer Care Ontario recommendations on the Role of Patient and Disease Factors in Adjuvant Systemic Therapy Decision Making for Early-Stage, Operable Breast Cancer., Methods: Two phase III trials-the Trial Assigning Individualized Options for Treatment (TAILORx) in women with hormone receptor-positive, node-negative tumors and the Microarray in Node-Negative and 1 to 3 Positive Lymph Node Disease May Avoid Chemotherapy (MINDACT) trial-provided the evidence for this update., Updated Recommendations: Shared decision making between clinicians and patients is appropriate for adjuvant systemic therapy for breast cancer. For patients older than age 50 years and whose tumors have Onco type DX recurrence scores less than 26, and for patients age 50 years or younger whose tumors have Onco type DX recurrence scores less than 16, there is little to no benefit from chemotherapy. Clinicians may offer endocrine therapy alone for these patients. For patients age 50 years or younger with recurrence scores of 16 to 25, clinicians may offer chemoendocrine therapy. Patients with recurrence scores greater than 30 should be considered candidates for chemoendocrine therapy. Based on informal consensus, the Panel recommends that oncologists may offer chemoendocrine therapy to patients with Onco type DX scores of 26 to 30.The MammaPrint assay could be used to guide decisions on withholding adjuvant systemic chemotherapy in patients with hormone receptor-positive lymph node-negative breast cancer and in select patients with lymph node-positive cancers. In both patients with node-positive and node-negative disease, evidence of clinical utility of the MammaPrint assay was only apparent in those determined to be at high clinical risk; the Panel thus did not recommend use of MammaPrint assay in patients determined to be at low clinical risk. Remaining recommendations from the 2016 ASCO guideline endorsement are unchanged.Additional information is available at www.asco.org/breast-cancer-guidelines.

Purpose: This focused update addresses the use of Onco type DX in guiding decisions on the use of adjuvant systemic therapy., Methods: ASCO uses a signals approach to facilitate guideline updating. For this focused update, the publication of the Trial Assigning Individualized Options for Treatment (TAILORx) evaluating noninferiority of endocrine therapy alone versus chemoendocrine therapy for invasive disease-free survival in women with Onco type DX scores provided a signal. An expert panel reviewed the results of TAILORx along with other published literature on the Onco type DX assay to assess for evidence of clinical utility., Updated Recommendations: For patients with hormone receptor-positive, axillary node-negative breast cancer whose tumors have Onco type DX recurrence scores of less than 26, there is little to no benefit from chemotherapy, especially for patients older than age 50 years. Clinicians may recommend endocrine therapy alone for women older than age 50 years. For patients 50 years of age or younger with recurrence scores of 16 to 25, clinicians may offer chemoendocrine therapy. Patients with recurrence scores greater than 30 should be considered candidates for chemoendocrine therapy. Based on informal consensus, the panel recommends that oncologists may offer chemoendocrine therapy to these patients with recurrence scores of 26 to 30. Additional information can be found at www.asco.org/breast-cancer-guidelines.

Purpose: To better understand the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS v1.1) and the ASCO Value Framework Net Health Benefit score version 2 (ASCO-NHB v2), ESMO and ASCO collaborated to evaluate the concordance between the frameworks when used to assess clinical benefit attributable to new therapies., Methods: The 102 randomized controlled trials in the noncurative setting already evaluated in the field testing of ESMO-MCBS v1.1 were scored using ASCO-NHB v2 by its developers. Measures of agreement between the frameworks were calculated and receiver operating characteristic curves used to define thresholds for the ASCO-NHB v2 corresponding to ESMO-MCBS v1.1 categories. Studies with discordant scoring were identified and evaluated to understand the reasons for discordance., Results: The correlation of the 102 pairs of scores for studies in the noncurative setting is estimated to be 0.68 (Spearman's rank correlation coefficient; overall survival, 0.71; progression-free survival, 0.67). Receiver operating characteristic curves identified thresholds for ASCO-NHB v2 for facilitating comparisons with ESMO-MCBS v1.1 categories. After applying pragmatic threshold scores of 40 or less (ASCO-NHB v2) and 2 or less (ESMO-MCBS v1.1) for low benefit and 45 or greater (ASCO-NHB v2) and 4 to 5 (ESMO-MCBS v1.1) for substantial benefit, 37 discordant studies were identified. Major factors that contributed to discordance were different approaches to evaluation of relative and absolute gain for overall survival and progression-free survival, crediting tail of the curve gains, and assessing toxicity., Conclusion: The agreement between the frameworks was higher than observed in other studies that sought to compare them. The factors that contributed to discordant scores suggest potential approaches to improve convergence between the scales.

Purpose To update key recommendations of the ASCO guideline adaptation of the Cancer Care Ontario guideline on the selection of optimal adjuvant chemotherapy regimens for early breast cancer and adjuvant targeted therapy for breast cancer. Methods An Expert Panel conducted targeted systematic literature reviews guided by a signals approach to identify new, potentially practice-changing data that might translate to revised practice recommendations. Results The Expert Panel reviewed phase III trials that evaluated adjuvant capecitabine after completion of standard preoperative anthracycline- and taxane-based combination chemotherapy by patients with early-stage breast cancer HER2-negative breast cancer with residual invasive disease at surgery; the addition of 1 year of adjuvant pertuzumab to combination chemotherapy and trastuzumab for patients with early-stage, HER2-positive breast cancer; and the use of neratinib as extended adjuvant therapy for patients after combination chemotherapy and trastuzumab-based adjuvant therapy with early-stage, HER2-positive breast cancer. Recommendations Patients with early-stage HER2-negative breast cancer with pathologic, invasive residual disease at surgery following standard anthracycline- and taxane-based preoperative therapy may be offered up to six to eight cycles of adjuvant capecitabine. Clinicians may add 1 year of adjuvant pertuzumab to trastuzumab-based combination chemotherapy in patients with high-risk, early-stage, HER2-positive breast cancer. Clinicians may use extended adjuvant therapy with neratinib to follow trastuzumab in patients with early-stage, HER2-positive breast cancer. Neratinib causes substantial diarrhea, and diarrhea prophylaxis must be used. Additional information can be found at www.asco.org/breast-cancer-guidelines .

Purpose To provide guidance regarding the practical assessment and management of vulnerabilities in older patients undergoing chemotherapy. Methods An Expert Panel was convened to develop clinical practice guideline recommendations based on a systematic review of the medical literature. Results A total of 68 studies met eligibility criteria and form the evidentiary basis for the recommendations. Recommendations In patients ≥ 65 years receiving chemotherapy, geriatric assessment (GA) should be used to identify vulnerabilities that are not routinely captured in oncology assessments. Evidence supports, at a minimum, assessment of function, comorbidity, falls, depression, cognition, and nutrition. The Panel recommends instrumental activities of daily living to assess for function, a thorough history or validated tool to assess comorbidity, a single question for falls, the Geriatric Depression Scale to screen for depression, the Mini-Cog or the Blessed Orientation-Memory-Concentration test to screen for cognitive impairment, and an assessment of unintentional weight loss to evaluate nutrition. Either the CARG (Cancer and Aging Research Group) or CRASH (Chemotherapy Risk Assessment Scale for High-Age Patients) tools are recommended to obtain estimates of chemotherapy toxicity risk; the Geriatric-8 or Vulnerable Elders Survey-13 can help to predict mortality. Clinicians should use a validated tool listed at ePrognosis to estimate noncancer-based life expectancy ≥ 4 years. GA results should be applied to develop an integrated and individualized plan that informs cancer management and to identify nononcologic problems amenable to intervention. Collaborating with caregivers is essential to implementing GA-guided interventions. The Panel suggests that clinicians take into account GA results when recommending chemotherapy and that the information be provided to patients and caregivers to guide treatment decision making. Clinicians should implement targeted, GA-guided interventions to manage nononcologic problems. Additional information is available at www.asco.org/supportive-care-guidelines .

Purpose To update, in collaboration with Cancer Care Ontario (CCO), key recommendations of the American Society of Clinical Oncology (ASCO) guideline on the role of bone-modifying agents (BMAs) in metastatic breast cancer. This focused update addressed the new data on intervals between dosing and the role of BMAs in control of bone pain. Methods A joint ASCO-CCO Update Committee conducted targeted systematic literature reviews to identify relevant studies. Results The Update Committee reviewed three phase III noninferiority trials of dosing intervals, one systematic review and meta-analysis of studies of de-escalation of BMAs, and two randomized trials of BMAs in control of pain secondary to bone metastases. Recommendations Patients with breast cancer who have evidence of bone metastases should be treated with BMAs. Options include denosumab, 120 mg subcutaneously, every 4 weeks; pamidronate, 90 mg intravenously, every 3 to 4 weeks; or zoledronic acid, 4 mg intravenously every 12 weeks or every 3 to 4 weeks. The analgesic effects of BMAs are modest, and they should not be used alone for bone pain. The Update Committee recommends that the current standard of care for supportive care and pain management-analgesia, adjunct therapies, radiotherapy, surgery, systemic anticancer therapy, and referral to supportive care and pain management-be applied. Evidence is insufficient to support the use of one BMA over another. Additional information is available at www.asco.org/breast-cancer-guidelines and www.asco.org/guidelineswiki .