Chemotherapy Side Effects and Gene Expression

Chemotherapy Side Effects

• Taxanes are associated with hypersensitivity reactions, peripheral neuropathy, myalgias, and arthralgias for a few days following the infusion.
• Cyclophosphamide is associated with hemorrhagic cystitis, myelosuppression, nausea/vomiting, and alopecia.
• Alkylating agents are associated with a risk of secondary leukemia.

Gene Expression Assays

• Gene expression assays (Oncotype DX and MammaPrint) can identify patients who could avoid chemotherapy without altering the disease prognosis.
• Genomic analyses may play an important role in improving risk stratification and determining chemotherapy benefit.

Adjuvant Biologic Therapy (Trastuzumab)

• Trastuzumab is indicated for treatment of breast cancer in patients who have tumors that overexpress HER-2.
• Trastuzumab should not be given concurrently with the anthracyclines due to increased risk of cardiotoxicity.
• Common adverse effects of trastuzumab include infusion-related reactions (e.g., chills).
• Rare adverse effects of trastuzumab include pulmonary reactions (dyspnea, pulmonary infiltrates, non-cardiogenic pulmonary edema, and hypoxia).

Adjuvant Endocrine Therapy

• Hormonal therapies studied in the treatment of early breast cancer include SERMs, oophorectomy, ovarian irradiation, LHRH agonists, and aromatase inhibitors (AIs).
• Tamoxifen is a SERM that is anti-estrogenic in breast cancer cells but has estrogenic properties in other tissues and organs.
• Administration of tamoxifen should begin after completion of chemotherapy.
• Patients receiving tamoxifen should be counseled about warning signs of endometrial cancer and thromboembolism.

Menopausal Status and Endocrine Therapy

• In premenopausal women, the use of LHRH agonists or other means of ovarian ablation have been shown beneficial in the adjuvant setting.
• AIs are recommended as the endocrine therapy of choice for postmenopausal women.
• Anastrozole and letrozole are non-steroidal compounds that exhibit reversible, competitive inhibition of aromatase.
• Exemestane is a steroidal compound that binds irreversibly to aromatase, forming a covalent bond.

Treatment of Stage III Breast Cancer

• Treatment of stage III breast cancer generally consists of a combination of surgery, radiation, and systemic therapy administered in an aggressive approach with the treatment goal of a cure.
• Systemic relapse and death are common.
• Neo-adjuvant chemotherapy is used to render inoperable tumors resectable, even with the possibility of breast-conserving surgery.
• Chemotherapy regimens used in stage III breast cancer are similar to those used in the adjuvant setting.