# Recommendations
Chemotherapy for Non-Metastatic Breast Cancer 1. The decision for adjuvant/neoadjuvant chemotherapy should be guided by the subtype of breast cancer (hormone receptor -positive/human epidermal growth factor receptor 2 negative, HER2-positive, and triple negative (TN)], prognosis, benefits (absolute gains in disease free survival  and overall survival ), toxicity risks, overall health of patient, and preference of patient. 1,2 (Level of Evidence: I, Strength of Recommendation: A) 2. Individualized prognosis and expected benefit from systemic treatments, including chemotherapy, can be estimated using an online calculator such as NHS Predict which considers: patient age and menopausal status, presentation (screen detected versus symptomatic), tumour size, axillary lymph node status, and the status of estrogen receptor (ER), HER2 and Ki67 if known. 3 In some patients with ER-positive/HER2-negative early breast cancer, prognosis +/-benefit of chemotherapy can be estimated from gene expression profile (GEP) testing. 4,5 Figure 1 outlines OncotypeDX testing eligibility in Alberta. 3. Figure 2 outlines an approach to chemotherapy decision-making for HR-positive/HER2-negative breast cancer, Figure 3 for HER2-positive, and Figure 4 for TN. 1,2, (Level of Evidence: I, Strength of Recommendation: A) 4. As for the decision to use chemotherapy, the choice of regimen should also be guided by prognosis, benefits (absolute gains in DFS and OS where applicable), toxicity risks, overall health of patient, and preference of patient. In addition to the listed adjuvant chemotherapy regimens, other evidence-based options exist, and may be used based on clinical discretion and in review with multidisciplinary breast cancer tumour board. 5. Delays in initiating adjuvant chemotherapy should be avoided. 10 Adjuvant chemotherapy should be started, as soon as surgical healing has been completed and ideally not later than 12 weeks following surgery. 1 (Level of Evidence: I, Strength of Recommendation: A) 6. In patients with known cardiac dysfunction or significant cardiac risk, a non-anthracycline adjuvant chemotherapy regimen is preferred. (Level of Evidence: I, Strength of Recommendation: A) If trastuzumab is required, consider upfront referral to cardiology.  (Level of Evidence: V, Strength of Recommendation: A) 7. Offer young women referral to a fertility clinic prior to initiation of adjuvant systemic therapies if future pregnancies are potentially desired. 14 (Level of Evidence: V, Strength of Recommendation: A) In addition to standard fertility preservation methods or if standard fertility preservation methods are not feasible, use of a luteinizing hormone-releasing hormone (LHRH) agonist during chemotherapy can be discussed with the goal of reducing the likelihood of chemotherapy-induced ovarian insufficiency. 14,15 (Level of Evidence: II, Strength of Recommendation: B) 8. Use primary granulocyte colony-stimulating factor (GCSF) prophylaxis with dose dense regimens and regimens in which the risk of febrile neutropenia is greater than or equal to 20%. 16 Use secondary GCSF prophylaxis if there was a neutropenic complication in previous chemotherapy cycle and if dose-reduction is expected to compromise oncologic outcomes. 16 (Level of Evidence: I, Strength of Recommendation: A)

# Chemotherapy for Hormone Receptor-Positive/HER2-Negative Breast Cancer
- Decision-making about chemotherapy in this group is complex as there is a wide range for prognosis, stage for stage, driven by underlying tumour biology. The American Joint Committee on Cancer (AJCC) 8 th Edition incorporates prognostic stage grouping for hormone receptorpositive breast cancer that not only considers T-stage and N-stage, but also grade, ER-status, progesterone receptor (PR)-status, and the OncotypeDX Recurrence Score (RS) (if less than 11) when available. 17 2. Favourable tumour biology is suggested by a luminal A molecular signature or luminal A-like characteristics (high ER & PR expression AND grade 1-2 and/or low Ki67 score). 1, 2 3. Less favourable tumour biology is suggested by a luminal B molecular signature or luminal B-like characteristics (high or low ER expression AND low PR expression or PR-negative AND grade 2-3 and/or higher Ki67 score). 1, 2 4. The predicted absolute overall survival benefit of chemotherapy is low for most patients with favourable tumour biology. However, the predicted absolute overall survival benefit of chemotherapy can be quite variable for patients with less favourable tumour biology. NHS Predict, and in eligible patients, OncotypeDX testing, can aid with prognostication and chemotherapy decision-making. 5,18 

# Lower risk
T1a/b and node negative or Luminal A-like 1 or OncotypeDX lower risk 3 Higher risk T >3cm &/or node positive and Luminal B-like 2 or OncotypeDX higher risk 4 Neoadjuvant chemotherapy 6 DC, FEC-D, ddAC-P   

# Development and Revision History
This guideline was reviewed and endorsed by the Alberta Provincial Breast Tumour Team. Members include surgical oncologists, radiation oncologists, medical oncologists, nurses, pathologists, and pharmacists. Evidence was selected and reviewed by a working group comprised of members from the Alberta Provincial Breast Tumour Team, external participants identified by the Working Group Lead, and a methodologist from the Guideline Resource Unit. A detailed description of the methodology followed during the guideline development process can be found in the Guideline Resource Unit Handbook.
This guideline was originally developed in April 2014 and updated in April 2021.

# Levels of Evidence

# I
Evidence