Treatment Modalities and Management of Side Effects
Local therapy
Breast-conserving surgery plus radiation gives survival equivalent to mastectomy when margins are clear. Contraindications include multicentric disease, prior chest radiation, pregnancy (at least in the first trimester), and persistently positive margins. Sentinel node biopsy stages the axilla with less morbidity than axillary dissection.
Systemic therapy by subtype
Hormone receptor-positive, HER2-negative disease: endocrine therapy with or without chemotherapy, plus CDK4/6 inhibitors in advanced or high-risk early disease. HER2-positive disease: trastuzumab and pertuzumab with a taxane. Triple-negative disease: chemotherapy, with immunotherapy in selected cases. BRCA-associated disease: PARP inhibitors. Neoadjuvant therapy is used for locally advanced disease and to guide postoperative treatment in HER2-positive and triple-negative disease.
Endocrine therapy rules
Tamoxifen works in any menopausal state and is used for 5-10 years; it raises venous thromboembolism and endometrial cancer risk and causes hot flashes. Aromatase inhibitors only work in postmenopausal women and cause arthralgia and bone loss, so baseline and follow-up bone density matter. Ovarian suppression is added for high-risk premenopausal women.
Key toxicities
Anthracyclines cause cumulative cardiomyopathy; dexrazoxane is a cardioprotectant. Trastuzumab causes usually reversible LVEF decline, monitored at baseline and every few months. Taxanes cause peripheral neuropathy. Cyclophosphamide can cause hemorrhagic cystitis, prevented with hydration. Radiation causes dermatitis and fatigue.
Worked example. A premenopausal woman with HER2-positive node-positive disease receives neoadjuvant taxane, trastuzumab, pertuzumab, and carboplatin; LVEF is checked at baseline and every 3 months. She is not given an aromatase inhibitor.