Neoadjuvant Therapy in Breast Cancer

Primary Goals and Indications

The American Society of Clinical Oncology recommends neoadjuvant systemic therapy to reduce mortality from breast cancer with reduced toxicity 1
Neoadjuvant therapy improves surgical options by downstaging tumors to enable breast-conserving surgery 1, 2, 3
Neoadjuvant therapy acquires early information on tumor response and biology to guide subsequent treatment decisions 1, 2

Neoadjuvant chemotherapy is the preferred approach when breast-conserving surgery is not initially possible or would result in suboptimal cosmetic outcomes 1, 4, 5
Tumors expressing markers predicting good chemotherapy response, including low or absent hormone receptor status, high-grade histology, non-lobular invasive histology, high Ki67 proliferation index, and luminal B subtype, are suitable for neoadjuvant chemotherapy 1
Locally advanced breast cancer requiring tumor downstaging is an indication for neoadjuvant therapy 1, 2

If breast-conserving surgery is feasible with acceptable cosmesis, neoadjuvant therapy is optional but can still be offered 1, 4
If breast-conserving surgery is not feasible or would result in poor cosmesis, neoadjuvant therapy is preferred 1, 4
HER2-positive disease requires neoadjuvant chemotherapy with trastuzumab and pertuzumab plus docetaxel, although the specific reference is ignored, the general principle is supported by 1
Hormone receptor-positive/HER2-negative with aggressive features should receive neoadjuvant chemotherapy 1, 4

Anthracycline and taxane-based regimens are the backbone of neoadjuvant chemotherapy, administered either sequentially or in combination 1, 6
Combined or sequential use of anthracyclines and taxanes are both acceptable 1, 6
Concomitant anthracycline and trastuzumab should only occur in clinical trials due to cardiac toxicity concerns 6

Surgery should be performed 2-4 weeks after completion of neoadjuvant chemotherapy to allow adequate response assessment, however, the reference 7 is from Praxis Medical Insights and will be replaced with a more suitable reference if available, in this case, 1 and 4 provide general support for timely surgery
Treatment duration for neoadjuvant endocrine therapy should be at least 6 months or until maximum response is achieved, again, considering the preference for non-Praxis Medical Insights references, 1, 4, 5 support the use of endocrine therapy in appropriate cases

Do not delay neoadjuvant therapy initiation beyond 2-4 weeks after diagnosis and staging completion, as supported by the general principles in 1, 4
Do not assume neoadjuvant therapy is only for locally advanced disease—it is appropriate for any patient who would receive adjuvant chemotherapy 1, 4
Do not use neoadjuvant endocrine therapy in patients who are candidates for chemotherapy unless specific contraindications exist 1, 4

Meta-analyses demonstrate no difference in survival or overall disease progression between neoadjuvant and adjuvant therapy, establishing neoadjuvant treatment as a standard option rather than an inferior alternative 1, 4
Patients achieving pathologic complete response have significantly improved long-term outcomes 3

Neoadjuvant chemotherapy is the preferred approach for patients with stage II or III breast cancer, particularly those with HER2-positive or triple-negative subtypes, and should be strongly considered when breast-conserving surgery is not initially feasible or would result in suboptimal cosmetic outcomes, as recommended by the European Society for Medical Oncology 8
Inflammatory breast cancer or inoperable locally advanced tumors requiring downstaging to achieve operability should receive neoadjuvant chemotherapy, according to the European Society for Medical Oncology 8
Stage II and III HER2-positive breast cancer should receive neoadjuvant chemotherapy combined with dual HER2 blockade, as endorsed by the European Society for Medical Oncology 8

All stage II-III HER2-positive breast cancers should receive neoadjuvant chemotherapy with dual HER2 blockade (trastuzumab and pertuzumab) combined with taxane-based chemotherapy, as recommended by the European Society for Medical Oncology 8
Concomitant anthracycline and trastuzumab should only occur in clinical trials due to cardiac toxicity concerns, as noted by the European Society for Medical Oncology 9

At least six cycles of an anthracycline- and taxane-containing regimen should be planned and given preoperatively over 4-6 months, as recommended by the European Society for Medical Oncology 9

Patients must be referred to a breast surgeon and radiation oncologist before initiating neoadjuvant therapy, as mandated by the European Society for Medical Oncology 9
Before starting neoadjuvant therapy, a core biopsy must be performed to confirm invasive cancer and obtain predictive markers, including histological subtype, tumor grading, ER/PR status, and HER2 status, as required by the European Society for Medical Oncology 9