Breast Cancer Evidence Navigator

Historical surrogate classification: St Gallen 2013 used a laboratory-dependent “low” Ki-67; <14% correlated best with PAM50 Luminal A in one reference laboratory, and PR ≥20% helped identify Luminal A-like disease.

Modern interpretation: reproducibility is best at the extremes. The International Ki67 Working Group / St Gallen 2021 framework regards approximately ≤5% as clearly low and ≥30% as clearly high in the appropriate ER+/HER2− early-disease context. Most tumours fall between these values, where a universal treatment cutoff is not established.

The Navigator therefore displays both the historical surrogate label and the modern certainty band instead of disguising convention as biology.

They measure different gene sets, use different algorithms and were validated for different questions/populations. They are not interchangeable scores.

ASCO supports selected use in early ER-positive/HER2-negative disease, with important restrictions by menopausal status and nodal burden. None is recommended to guide adjuvant chemotherapy in HER2-positive or triple-negative disease.

ESMO Precision Oncology Working Group 2025: a mortality/clinical-utility-based mainstream breast panel centres on BRCA1, BRCA2, PALB2, RAD51C, RAD51D, BRIP1 and TP53 (TP53 particularly for breast cancer diagnosed under age 40).

This deliberately differs from broad “pan-cancer” panels. ESMO recommends that rare syndromic genes such as PTEN, STK11, NF1 and CDH1 be considered downstream after expert review when the phenotype/family history suggests the syndrome. ATM and CHEK2 carry breast-cancer risk information but were not included in that 2025 mortality-utility core panel.

ESMO 2023: SLNB remains the standard axillary surgery for clinically node-negative early breast cancer.

ASCO 2025: after SOUND/INSEMA, routine SLNB can be omitted in a much narrower population: postmenopausal age ≥50, small ≤2 cm unifocal grade 1–2 HR+/HER2− invasive ductal cancer, negative/concordant preoperative axillary ultrasound, planned endocrine therapy and breast-conserving treatment, when finding a positive SLN would not change treatment.

The Navigator therefore labels this as guideline evolution / international divergence. It does not silently overwrite the selected European/national practice context with a US recommendation.

Invasive cancer + whole-breast RT: “no ink on tumour” is the established adequate-margin standard; routinely seeking wider negative margins does not improve local control.

Pure DCIS + whole-breast RT: a 2 mm negative margin is the consensus standard associated with low ipsilateral recurrence. A negative margin narrower than 2 mm does not automatically mandate mastectomy or re-excision; clinical judgment matters.

A positive margin remains different from a merely narrow negative margin.

Endocrine therapy depends primarily on hormone-receptor biology and menopausal context.

Chemotherapy depends on recurrence risk and expected benefit; in selected ER+/HER2− early disease, multigene assays can refine that question.

Adjuvant CDK4/6 inhibition is an escalation layer for defined higher-risk HR+/HER2− disease, and the eligible populations differ between abemaciclib and ribociclib.

Olaparib requires a germline BRCA1/2 pathogenic variant plus HER2-negative high-risk early disease after chemotherapy; “BRCA-mutated” alone is not enough.

HER2-directed therapy uses the conventional HER2-positive category, not the HER2-low descriptor used for some antibody-drug conjugates in advanced disease.

Pembrolizumab in early TNBC is a high-risk early-disease strategy and does not require the metastatic PD-L1 CPS threshold.

The antiemetic prescription is derived from the emetogenic risk of the complete regimen. Anthracycline + cyclophosphamide is highly emetogenic in breast cancer; carboplatin AUC ≥5 sits at the high end of moderate risk; taxanes alone are much less emetogenic.

The tool therefore separates acute prophylaxis, delayed prophylaxis and rescue, and points back to MASCC/ESMO rather than attaching one universal antiemetic cocktail to every chemotherapy.

Whole-breast/chest-wall irradiation addresses residual microscopic risk in the breast or chest wall after surgery.

Regional nodal irradiation is a separate decision driven mainly by nodal involvement, burden and response to neoadjuvant therapy.

Boost changes dose to the tumour bed, principally trading better local control against greater fibrosis/cosmetic burden in selected higher-local-risk situations.

Partial-breast irradiation is a de-escalated target-volume strategy for selected low-risk patients; it is not simply a shorter whole-breast schedule.

Fractionation is yet another question: once the target is chosen, the same target may often be treated using moderate or, in selected situations, ultra-hypofractionation.

For treated early breast cancer, ESMO recommends clinical follow-up and breast imaging. In an asymptomatic patient, routine blood counts, chemistry, tumour markers and other systemic imaging are not recommended. New symptoms or examination findings should trigger targeted investigation.

This is a deliberate rule in the Navigator: absence of routine imaging is not undertreatment. Imaging becomes appropriate when there is a clinical question whose answer can change management.