Adjuvant Chemotherapy for Stage IA (pT1cN0M0) Breast Cancer
The decision to use adjuvant chemotherapy in Stage IA (pT1cN0M0) breast cancer depends critically on tumor biology—specifically hormone receptor (ER/PR) and HER2 status—rather than stage alone, with most luminal A-like tumors not requiring chemotherapy except those with high disease burden. 1
Decision Framework Based on Tumor Biology
For ER/PR-Positive, HER2-Negative Disease (Luminal-like)
Most patients with luminal A-like tumors (pT1cN0M0) do not require chemotherapy. 1 The Pan-Asian adapted ESMO guidelines explicitly state that luminal A-like tumors do not require chemotherapy except those with high disease burden 1, and a pT1c tumor (1.1-2.0 cm) with node-negative status typically represents low disease burden.
When Genomic Testing Should Be Used:
In cases of uncertainty regarding chemotherapy indications after considering all clinical and pathological factors, gene expression assays such as Oncotype DX, MammaPrint, Prosigna (PAM50), EndoPredict, or Breast Cancer Index can be used. 1
For ER/PR-positive, HER2-negative, node-negative breast cancer, the 21-gene recurrence score (Oncotype DX) may be used to guide decisions on adjuvant systemic chemotherapy (evidence quality: high, strength of recommendation: strong). 1
The PAM50 risk of recurrence score (Prosigna) may be used in conjunction with other clinicopathologic variables to guide decisions (evidence quality: high, strength of recommendation: strong). 1
The 12-gene risk score (EndoPredict) may be used to guide chemotherapy decisions (evidence quality: intermediate, strength of recommendation: moderate). 1
The Breast Cancer Index may be used to guide decisions on adjuvant systemic therapy (evidence quality: intermediate, strength of recommendation: moderate). 1
For Triple-Negative Breast Cancer (TNBC)
Patients with TNBC should receive chemotherapy, with the possible exception of low-risk 'special histological subtypes' such as secretory juvenile or adenoid cystic carcinomas. 1 Even at pT1cN0M0 stage, TNBC typically warrants chemotherapy due to its aggressive biology and lack of targeted therapy options.
For HER2-Positive Disease
HER2-positive cancers should be treated with chemotherapy plus anti-HER2 therapy, with the possible exception of selected cases with very low risk, such as T1aN0 tumors. 1
For pT1c (1.1-2.0 cm) tumors, trastuzumab should be considered for patients with HER2-positive node-negative tumors ≥1 cm (category 1). 1
Paclitaxel plus trastuzumab may be considered for patients with low-risk stage I, HER2-positive disease, particularly those not eligible for other standard adjuvant regimens because of comorbidities. 1
Timing and Sequencing Considerations
Adjuvant systemic treatment should preferably start within 3-6 weeks after surgery. 1
If chemotherapy and radiation therapy are to be used, chemotherapy should usually precede radiation therapy. 1
Chemotherapy and endocrine therapy used as adjuvant therapy should be given sequentially with endocrine therapy after chemotherapy. 1
Common Pitfalls to Avoid
Do not base the chemotherapy decision on stage alone—a pT1cN0M0 tumor can be TNBC requiring chemotherapy or luminal A-like requiring only endocrine therapy. 1
Do not use the 21-gene recurrence score (Oncotype DX) for HER2-positive or triple-negative breast cancer (evidence quality: insufficient, strength of recommendation: strong). 1
Do not use MammaPrint (70-gene assay) to guide chemotherapy decisions in ER/PR-positive, HER2-negative disease (evidence quality: intermediate, strength of recommendation: moderate). 1
For luminal B-like HER2-negative patients, chemotherapy use depends on individual risk of recurrence, presumed responsiveness to endocrine therapy, and patient preferences. 1
Endocrine Therapy Mandate
All luminal-like cancers should be treated with endocrine therapy regardless of whether chemotherapy is given. 1 This is non-negotiable for ER/PR-positive disease and represents the cornerstone of treatment for hormone receptor-positive breast cancer. 2