Evidence-Based Consensus on the Diagnosis and Treatment of Advanced HER2-Positive and HER2-Low Breast Cancer in Colombia

Abstract

Background/Objectives: The management of advanced HER2-positive and HER2-low breast cancer is evolving rapidly. This study aimed to generate national, evidence-based clinical recommendations for Colombia, addressing the lack of standardized local guidance. Methods: A systematic literature search (2020–2024) was conducted. The evidence was evaluated using AGREE II, RoB 2, ROBINS-I, and JBI tools. Recommendations were developed using the GRADE approach and a structured modified Delphi consensus process involving 34 national experts. Results: A total of 22 clinical recommendations were formulated. These address HER2 quantification and reporting, first-line and subsequent-line therapy, and management of brain metastases. Five recommendations (23%) were classified as strong, supported by high-certainty evidence, while 17 (77%) were conditional, reflecting the need for adaptation to local contexts and resource availability. Conclusions: This consensus provides updated, context-specific clinical guidance to optimize the care of patients with advanced HER2-positive and HER2-low breast cancer in Colombia. The recommendations are designed to standardize care, improve patient outcomes, and promote equitable access to innovative therapies within the Colombian healthcare system.

1. Introduction

Breast cancer (BC) is the most common neoplasm in women globally and ranks as the second most frequent cancer when considering both sexes. According to recent data from GLOBOCAN 2022, 2,296,840 new cases were reported, representing 11.5% of all cancers and 23.8% of cancers in women. Moreover, it caused 666,103 deaths, making it the fourth leading cause of cancer-related mortality worldwide. The five-year prevalence reached 8.17 million cases, highlighting its significant global public health burden [1].

In Colombia, BC is also the most frequent neoplasm in women, with an estimated 17,018 new cases in 2022, accounting for 27.7% of female cancer diagnoses. During the same period, annual mortality from this cause was 4752 deaths, positioning it as the fourth leading cause of cancer-related death in the country and the first among women [1].

Advances in molecular biology have enabled the identification of breast cancer subtypes with therapeutic relevance, particularly those defined by the expression of the human epidermal growth factor receptor 2 (HER2). It is estimated that 20–25% of cases are HER2-positive, and among these, approximately half also express hormone receptors [2]. Additionally, a newly described subtype known as HER2-low, characterized by HER2 IHC 1+ or 2+ with a negative in situ hybridization (ISH) result, accounts for approximately 50% of all breast cancer cases [3].

The availability of antibody-drug conjugates such as trastuzumab deruxtecan (T-DXd) has demonstrated clinical benefits in patients with advanced HER2-low disease, improving both overall survival and progression-free survival [4]. These advances underscore the need for rigorous and standardized HER2 testing and pathological characterization as recommended by ASCO/CAP guidelines and the ESMO consensus [5,6].

In this context, it is essential to have clinical recommendations adapted to the Colombian healthcare system to guide accurate diagnosis, molecular classification, and selection of targeted therapies. This national consensus, based on evidence and formal expert consensus, aims to optimize the care of patients with advanced HER2-positive and HER2-low breast cancer, improving clinical outcomes and promoting equitable access to innovative therapies.

2. Materials and Methods

2.1. Methodological Design

This clinical consensus was developed through a systematic and rigorous approach, integrating the best available scientific evidence and a formal consensus process using the modified Delphi method [7,8,9]. The objective was to formulate clinical recommendations contextualized to the Colombian healthcare system, based on up-to-date evidence and the experience of national experts in the management of advanced HER2 breast cancer.

2.2. Evidence Search and Selection

A systematic literature search was conducted in electronic databases (MEDLINE/PubMed, Embase, ClinicalKey, Scopus, and LILACS), complemented by manual searches in guideline repositories such as GIN, SIGN, NICE, and NCCN. The search covered publications from January 2020 to October 2024, with no language restrictions, prioritizing clinical practice guidelines, formal consensus documents, systematic reviews, and relevant primary studies on advanced breast cancer with HER2 expression [10,11,12,13,14,15].

Search strategies included controlled vocabulary (MeSH, Emtree) and free-text terms related to breast cancer, metastasis, recurrence, and HER2 expression, as well as filters by publication type. Full details of the search strategies are documented in Appendix A.

The systematic review component of this work was conducted and reported in accordance with the PRISMA 2020 guidelines. The completed PRISMA 2020 Checklist is provided as Supplementary Materials.

The systematic review component of this consensus was not registered, as it was performed to inform a formal expert consensus process rather than as an independent systematic review.

A descriptive summary of the key characteristics of the included evidence sources, including study type, geographic scope, target population, clinical setting, and main outcomes, is provided in Appendix B.

2.3. Eligibility Criteria

Publications that addressed the guiding questions of the consensus were included, with emphasis on clinical practice guidelines, consensus statements, systematic reviews, and clinically applicable primary studies. Narrative reviews, editorials, conference abstracts, and literature without methodological support or peer review were excluded.

2.4. Quality and Certainty Assessment of the Evidence

Methodological quality was assessed using standardized instruments according to the type of study: AGREE II for clinical guidelines [16,17], RoB 2 for randomized controlled trials [18], ROBINS-I [19], and Joanna Briggs Institute (JBI) [20] tools for non-randomized studies and formal consensus statements. Certainty of the evidence was graded according to GRADE as high, moderate, low, or very low [21]. Two reviewers independently extracted data using a standardized data extraction form. Any discrepancies were resolved through discussion or by consulting a third reviewer.

2.5. Consensus Process

The consensus was developed through a structured methodology based on the modified Delphi model [9], aiming to produce clinically relevant, feasible, and context-adapted recommendations for Colombia. A total of 34 national experts participated, including oncologists, pathologists, radiation oncologists, surgeons, internists, and other specialists, all with experience in advanced HER2 breast cancer (see Appendix C for the list of participants). Deliberations were conducted through virtual sessions and a final in-person meeting.

A detailed description of the expert panel composition, evidence preparation, and the modified Delphi consensus process is provided in Appendix D.

Each recommendation was approved by open voting using a 9-point Likert scale (1 = total disagreement; 9 = total agreement). Mean, median, and 95% confidence intervals (95% CI) of the scores were calculated. The following decision rules were applied:

• Include recommendation: if at least 80% of experts voted between 7 and 9, or if the median fell within that range.
• Exclude recommendation: if at least 80% voted between 1 and 3, or if the median was within that range.
• Further review: if no clear consensus was reached, additional group discussion and a second vote were conducted.

The results of the voting process and corresponding metrics are presented in Appendix E.

2.6. Strength of Recommendations

The classification of recommendations as strong or conditional was determined using the GRADE Evidence-to-Decision (EtD) framework, considering the following domains: priority of the problem, balance between benefits and risks, certainty of the evidence, resource use, feasibility, acceptability, and impact on equity [21].

Criteria for recommendation strength:

• Strong: if ≥95% of experts voted “yes” or “probably yes” in key domains (net benefit, high certainty, feasibility).
• Conditional: if that threshold was not reached or relevant uncertainty existed (low certainty, uncertain balance, or feasibility limitations).

This procedure ensured that all recommendations resulted from a transparent and systematic process, aligned with international standards [22], and adapted for implementation in resource-limited health systems such as Colombia’s.

3. Results

3.1. Evidence Search and Selection

The systematic search yielded a total of 644 references. After removing 115 duplicates, 529 titles and abstracts were screened, with 30 excluded for irrelevance. A total of 499 publications were assessed using the Rayyan^® platform, from which 46 studies were preselected for full-text evaluation. After applying the inclusion criteria, 17 were excluded, and 29 studies were included as direct evidence for the formulation of recommendations.

The direct evidence consisted of: 10 clinical practice guidelines (CPGs) [5,10,11,12,13,14,15,23,24,25], 1 formal ESMO consensus on HER2-low [6], 13 phase II–III clinical trials [4,26,27,28,29,30,31,32,33,34,35,36,37], 4 non-randomized studies [38,39,40,41], and 1 real-world observational study [42]. Additionally, 27 supplementary references were used for contextualization (citation chaining), without affecting the primary synthesis. The PRISMA diagram detailing the entire process is presented in Appendix F.

3.2. Assessment of Methodological Quality

The 10 clinical guidelines were assessed using AGREE II, with high methodological quality observed (≥60% score in rigor and clarity domains) [5,10,11,12,13,14,15,23,24,25]. The ESMO consensus was assessed with the JBI tool for formal guidelines, meeting all criteria for transparency, clinical expertise, conflict of interest management, and evidence-based formulation [6].

The 13 clinical trials were evaluated using RoB 2. Eight trials (e.g., DESTINY-Breast03/04, HER2CLIMB) showed low risk of bias [4,26,27,29,32,33,34,37], four raised some concerns [28,30,31,36], and one (LANTERN) was considered high risk due to methodological limitations [35].

The 4 non-randomized studies were evaluated with JBI tools. PERUSE and KAMILLA were rated as moderate quality [38,39], while DAISY and DESTINY-Breast01 were considered moderate to high quality despite the absence of a control group [40,41]. The observational study by Petit et al. was rated as having a serious risk of bias with ROBINS-I, due to uncontrolled confounding and missing data [42].

3.3. Certainty of the Evidence (GRADE)

The certainty of the evidence for each key question was assessed using the GRADE framework and is summarized in Appendix G. Certainty was classified as follows:

• High for recommendations supported by phase III RCTs with low risk of bias (e.g., CLEOPATRA, DESTINY-Breast03) [26,29,43].
• Moderate in contexts with clinical heterogeneity or limited precision (e.g., third-line treatment) [27,34,37].

This was not applicable for recommendations based solely on high-quality clinical guidelines and formal consensus documents, where GRADE was not applied, but inclusion was justified by methodological robustness [5,6,10].

3.4. Consensus Results and Strength of Recommendations

A total of 22 clinical recommendations were formulated. After group discussion and open voting:

• 17 recommendations (77%) were classified as conditional, due to low-to-moderate certainty or local feasibility constraints.
• 5 recommendations (23%) were classified as strong, with high certainty and immediate applicability.

Voting achieved ≥80% agreement in all cases. For conditional recommendations, the need for adaptation based on available resources and biomarker access was explicitly justified.

3.5. Clinical Recommendations

3.5.1. Question 1: Criteria for Quantifying and Reporting HER2 Expression

Evaluation of HER2 status is essential to determine eligibility for targeted therapies in advanced breast cancer. Direct evidence comes from high-quality international guidelines (ASCO/CAP 2018, ASCO/CAP 2023, ESMO 2023) [5,6,44], assessed using AGREE II. A recent formal consensus specifically addressing HER2-low was also included [6]. No primary studies were identified that modify current standards for HER2 quantification or reporting. The overall certainty of the evidence was considered high, due to methodological robustness, consistency across sources, and direct clinical applicability.

Guidelines recommend mandatory use of immunohistochemistry (IHC) with standardized scoring (0, 1+, 2+, 3+), complemented by in situ hybridization (ISH) to confirm HER2 amplification in IHC 2+ cases. Detailed reporting is essential to identify patients eligible for antibody-drug conjugates such as T-DXd, particularly in HER2-low and HER2-ultralow contexts [4]. Appropriate interpretation requires validated assays and adherence to international diagnostic algorithms.

Recommendations

• At the time of initial diagnosis of advanced breast cancer—whether newly diagnosed or recurrent—it is recommended to perform a biopsy of the primary tumor or metastatic lesion to assess estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) status (expert recommendation).
  Certainty of the evidence: high; strong recommendation.
• In patients with recurrent metastatic disease, HER2 status should be evaluated using tissue from the metastatic site, provided that such a sample is available (expert recommendation).
  Certainty of the evidence: high; strong recommendation.
• When reporting HER2 test results, pathologists should use nomenclature aligned with the ASCO/CAP 2018 and ESMO 2023 guidelines. Reports must include the HER2 immunohistochemistry (IHC) score (0, 1+, 2+, or 3+) to support the identification of patients with HER2-low or ultra-low expression (expert recommendation).
  Certainty of the evidence: high; strong recommendation.
• A validated HER2 test, consistent with current international guidelines, should be used to identify HER2 0, 1+, or HER2 2+/ISH non-amplified breast cancer. Appropriate assays for detecting HER2 protein include the Pathway 4B5 assay (used in the DB-04 study) or any other validated test deemed suitable by pathologists, based on the available evidence and practical considerations (expert recommendation).
  Certainty of the evidence: moderate; conditional recommendation.

3.5.2. Question 2: First-Line Treatment for Metastatic HER2-Positive Breast Cancer

First-line treatment for advanced HER2-positive breast cancer should optimize progression-free survival (PFS) and overall survival (OS), considering tolerability and access to targeted therapies. Direct evidence comes from high-quality phase III trials, such as CLEOPATRA, which demonstrated significant benefits with the combination of trastuzumab, pertuzumab, and docetaxel [43]. Additionally, studies such as PHILA and DESTINY-Breast03 provide evidence for the use of T-DXd in early relapses [26,32].

International guidelines support the combination of trastuzumab, pertuzumab, and a taxane as standard, followed by maintenance with the antibodies. However, clinical scenarios where this regimen is not feasible were identified, including chemotherapy contraindications, comorbidities, and early relapse after adjuvant treatment. In these contexts, evidence supports T-DXd as an alternative, and combinations with eribulin or endocrine therapy plus anti-HER2 according to hormone receptor status [14,28,45]. The overall certainty of evidence was high for the standard regimen and moderate for alternatives. All recommendations were classified as conditional due to the need for clinical adaptation.

Recommendations

• The combination of trastuzumab, pertuzumab, and a taxane is recommended as first-line treatment for patients with HER2-positive breast cancer, for up to six cycles of taxane therapy, unless contraindicated (expert recommendation).
  Certainty of the evidence: High. Recommendation: Conditional
• First-line treatment for metastatic HER2-positive breast cancer should include pertuzumab, trastuzumab, and docetaxel for up to six cycles, provided it is well tolerated. Maintenance therapy with pertuzumab and trastuzumab should then continue until disease progression, regardless of hormone receptor (HoR) status (expert recommendation).
  Certainty of the evidence: High. Recommendation: Conditional
• T-DXd is recommended as first-line treatment for patients who experience recurrence within six months of completing adjuvant or neoadjuvant therapy, or for those with contraindications to T-DM1 (Expert recommendation).
  Certainty of the evidence: High. Recommendation: Conditional
• The combination of eribulin, trastuzumab, and pertuzumab, followed by maintenance with trastuzumab and pertuzumab until disease progression or unacceptable toxicity, may be considered a valid alternative to the standard regimen of taxane, trastuzumab, and pertuzumab in patients with metastatic HER2-positive breast cancer (expert recommendation).
  Certainty of the evidence: Moderate. Recommendation: Conditional
• In patients with HER2-positive and HoR-negative breast cancer for whom chemotherapy is contraindicated, a HER2-targeted therapy strategy using trastuzumab plus pertuzumab is suggested. If taxanes are specifically contraindicated, another chemotherapy agent may be considered (expert recommendation).
  Certainty of the evidence: Moderate. Recommendation: Conditional
• In patients with HER2-positive and HoR-positive breast cancer in whom comorbidities, personal preferences, or functional status limit the use of chemotherapy, endocrine therapy—such as an aromatase inhibitor—combined with HER2-targeted therapy (trastuzumab plus pertuzumab) is suggested (expert recommendation).
  Certainty of the evidence: Moderate. Recommendation: Conditional

3.5.3. Question 3: Treatment After Disease Progression in Metastatic HER2-Positive Breast Cancer

Disease progression in HER2-positive breast cancer requires effective therapies in second-line and beyond. Direct evidence is mainly from high-quality phase III trials. The DESTINY-Breast03 trial demonstrated the superiority of T-DXd over T-DM1 in second-line, significantly improving progression-free and overall survival [26]. These findings led to T-DXd being positioned as the preferred treatment in this line.

In later lines, options include T-DM1, tucatinib combined with trastuzumab and capecitabine (HER2CLIMB) [27], and various anti-HER2-based regimens. However, evidence for third-line and beyond comes from studies with lower certainty, including post hoc analyses, observational studies, and clinical experience [30,38,39,40]. Overall certainty was high in second-line and moderate to low in later lines, supporting the classification of most recommendations as conditional.

Recommendations

• T-DXd is recommended as the preferred second-line treatment option for patients with HER2-positive breast cancer who experience disease progression after receiving a trastuzumab-based regimen (expert recommendation).
  Certainty of the evidence: High. Recommendation: Strong
• T-DXd is recommended as second-line therapy in patients with metastatic HER2-positive breast cancer who have progressed during or after treatment with trastuzumab, pertuzumab, and chemotherapy (expert recommendation).
  Certainty of the evidence: High. Recommendation: Strong
• T-DXd is recommended for patients with advanced HER2-positive breast cancer who have previously received trastuzumab, pertuzumab, and T-DM1 (expert recommendation).
  Certainty of the evidence: High. Recommendation: Conditional
• Continued anti-HER2 therapy beyond the second line is suggested in patients with metastatic breast cancer, as clinical benefit persists in third-line and later-line settings (expert recommendation).
  Certainty of the evidence: Moderate. Recommendation: Conditional
• For patients previously treated with T-DXd, the choice of subsequent treatment regimens, routes of administration, and toxicity management should be individualized through a shared decision-making process between the patient and medical team, as no direct comparative studies support a specific regimen (expert recommendation).
  Certainty of the evidence: Low. Recommendation: Conditional
• Options include the following:

  ○

  If the patient has not previously received trastuzumab emtansine (T-DM1) in the second line, a regimen including T-DM1 should be considered.

  Certainty of the evidence: High. Recommendation: Conditional

  ○

  Tucatinib in combination with trastuzumab and capecitabine may be offered as another treatment option for advanced disease.

  Certainty of the evidence: High. Recommendation: Conditional

  ○

  Neratinib combined with capecitabine may be offered.

  Certainty of the evidence: Low. Recommendation: Conditional

  ○

  Lapatinib plus trastuzumab may be offered.

  Certainty of the evidence: Low. Recommendation: Conditional

  ○

  Lapatinib plus capecitabine may be offered.

  Certainty of the evidence: High. Recommendation: Conditional

  ○

  Other chemotherapy and trastuzumab combinations may be considered—alternative regimens include the following:

  Certainty of the evidence: Moderate. Recommendation: Conditional

  ◾

  Vinorelbine + trastuzumab

  ◾

  Capecitabine + trastuzumab

  ◾

  Gemcitabine + trastuzumab

  ◾

  Eribulin + trastuzumab

  ◾

  Carboplatin + trastuzumab

  ◾

  Ixabepilone + trastuzumab

  ◾

  Liposomal doxorubicin + trastuzumab

  ○

  Margetuximab plus chemotherapy may be offered.

  Certainty of the evidence: Moderate. Recommendation: Conditional

  ○

  Hormonal therapy plus trastuzumab may be considered (for patients with estrogen receptor-positive [ER+] and/or progesterone receptor-positive [PgR+] disease).

  Certainty of the evidence: Moderate. Recommendation: Conditional

  ○

  Abemaciclib combined with trastuzumab and fulvestrant may be offered.

  Certainty of the evidence: Moderate. Recommendation: Conditional

• Trastuzumab emtansine (T-DM1) should be considered as a second-line treatment option for patients with HER2-positive breast cancer who have progressed after prior treatment with a taxane and trastuzumab, in settings where T-DXd is contraindicated (expert recommendation).
  Certainty of the evidence: High. Recommendation: Conditional
• The combination of tucatinib, capecitabine, and trastuzumab, as well as T-DXd, should be considered as second-line treatment options for selected patients with HER2-positive breast cancer and brain metastases (expert recommendation).
  Certainty of the evidence: Moderate. Recommendation: Conditional

3.5.4. Question 4: Treatment of Metastatic HER2-Low Breast Cancer

HER2-low is defined as IHC 1+ or 2+ with negative ISH, and represents an emerging subtype with specific therapeutic implications. The strongest evidence comes from the DESTINY-Breast04 trial, which showed that T-DXd significantly improves progression-free and overall survival in patients with HER2-low disease who had received prior chemotherapy and were refractory to endocrine therapy [4]. The certainty of evidence was high.

For HER2-low patients with hormone receptor-negative status, sacituzumab govitecan is a valid alternative, although with less robust comparative evidence. No direct trials compare T-DXd vs. sacituzumab govitecan. Selection is based on indirect analyses, clinical experience, and local availability [40,41,42]. Certainty of evidence was high for T-DXd in HER2-low HR+ population, and moderate for sacituzumab in HER2-low HR–. Recommendations were classified as strong or conditional based on certainty and applicability.

Recommendations

• Patients with metastatic HER2-low breast cancer (defined as IHC 1+ or IHC 2+/ISH-negative) who are hormone receptor-positive, have previously received cyclin-dependent kinase 4/6 (CDK4/6) inhibitors and at least one line of chemotherapy (or who experienced disease progression within six months after [neo] adjuvant chemotherapy), and are considered refractory to endocrine therapy, should be considered candidates for treatment with T-DXd (expert-adapted recommendation).
  Certainty of the evidence: Moderate. Recommendation: Conditional
• In patients with metastatic HER2-low breast cancer where both T-DXd and sacituzumab govitecan are available, T-DXd is preferred (expert-adapted recommendation).
  Certainty of the evidence: High. Recommendation: Strong
• Sacituzumab govitecan is suggested over T-DXd in patients with metastatic HER2-low breast cancer who are hormone receptor-negative (expert-adapted recommendation).

Certainty of the evidence: Moderate. Recommendation: Conditional

3.5.5. Question 5: Treatment of CNS Progression in HER2-Positive and HER2-Low Breast Cancer

Central nervous system (CNS) metastases are common in HER2-positive breast cancer, requiring integrated strategies. Direct evidence comes from the HER2CLIMB study, which demonstrated the efficacy of tucatinib, trastuzumab, and capecitabine in patients with brain metastases, improving PFS and OS, including in active CNS disease [27]. Observational evidence from KAMILLA also supports CNS efficacy of T-DXd, though with lower methodological strength [39].

In HER2-low, no specific trials addressed brain metastases, but indirect findings suggest T-DXd may be considered due to CNS penetration and activity. Certainty of evidence was high for tucatinib in HER2-positive and moderate for T-DXd in HER2-positive and HER2-low. Due to clinical heterogeneity and the need for individualized decisions, both recommendations were classified as conditional.

Recommendations:

• In patients with metastatic HER2-positive breast cancer who have achieved local control of the disease and have no evidence of systemic progression, it is suggested to consider continuing the previously established systemic treatment (expert consensus-based recommendation).
  Certainty of the evidence: Low. Recommendation: Conditional
• In patients for whom a change in systemic treatment is being considered:
  Certainty of the evidence: Moderate. Recommendation: Conditional

  ○

  For HER2-positive disease:

  ◾

  The combination of tucatinib, capecitabine, and trastuzumab is the preferred regimen, particularly in oligosymptomatic patients with limited disease.

  ◾

  T-DXd may also be considered.

  ○

  For HER2-low disease:

  ◾

  T-DXd may also be considered

Certainty of the evidence: Moderate. Recommendation: Conditional.

4. Discussion

This evidence-based clinical consensus provides updated guidelines for the diagnosis and treatment of advanced HER2-positive and HER2-low breast cancer in Colombia. The recommendations reflect the best available scientific evidence, contextualized through a structured consensus process involving national experts. Most recommendations were classified as conditional, reflecting both the need for adaptation to local settings and the clinical heterogeneity of the target population.

Therapeutic advances in HER2-positive breast cancer, such as the combination of trastuzumab, pertuzumab, and chemotherapy, have established a standard of care with a high level of certainty [14,43]. However, early relapses or contraindications to chemotherapy pose challenges in clinical practice, where alternatives like T-DXd have demonstrated efficacy in recent studies [26]. Likewise, the definition and management of the HER2-low subtype represent a paradigm shift in breast oncology. The DESTINY-Breast04 trial showed that patients with low HER2 expression can benefit from targeted therapies, expanding the available treatment options [4].

Implementation of these strategies in Colombia faces barriers related to access to precise diagnostic technologies, availability of high-cost therapies, and inequalities within the healthcare system. Therefore, this consensus emphasizes the need for detailed HER2 reporting and rational selection of validated tests, in accordance with international standards [5,6]. Moreover, clinical decision-making must consider feasibility, acceptability, and efficient use of resources, aligned with the GRADE and equity frameworks [46].

It is important to highlight that, although high-quality sources were used, not all clinical scenarios are supported by direct evidence. In such cases, recommendations were formulated based on prior consensus documents, observational data, and national clinical experience [38,39,40]. The consensus process ensured transparency and representativeness, with a high level of agreement among participants.

This consensus also identifies gaps in the evidence, such as the lack of specific studies on HER2-low with brain metastases, direct comparisons between antibody–drug conjugates, and the efficacy of combinations in specific subgroups. These issues should be addressed in future research involving Latin American populations. Furthermore, as a consensus guideline based on a narrative synthesis of the literature, this review does not provide the quantitative estimates of treatment effects that a formal meta-analysis would yield.

5. Conclusions

This consensus provides context-specific clinical recommendations for the management of advanced HER2-positive and HER2-low breast cancer, based on updated evidence and a formal expert consensus process. The recommendations are aligned with international guidelines but adapted to the realities of the Colombian healthcare system. Their implementation aims to optimize clinical decision-making, improve patient outcomes, and promote equitable access to innovative therapies.

This document serves as a reference tool for healthcare professionals, institutions, and decision-makers, aimed at standardizing care and reducing inequities in the treatment of advanced breast cancer in the country.