Based on the above studies, delaying radiation therapy for several months after breast-conserving surgery until the completion of adjuvant chemotherapy does not appear to have a negative impact on overall outcome. Additionally, initiating chemotherapy soon after breast-conserving therapy may be preferable for patients at high risk of distant dissemination.
In an unplanned analysis of patients treated on a phase III trial evaluating the benefit of adding trastuzumab in HER2/neu -positive breast cancer patients, there was no associated increase in acute adverse events or frequency of cardiac events in patients who received concurrent adjuvant radiation therapy and trastuzumab. Therefore, delivering radiation therapy concomitantly with trastuzumab appears to be safe and avoids additional delay in radiation therapy treatment initiation.
Timing of surgery
Several retrospective reviews have indicated that statistically significantly better DFS is achieved for premenopausal women with breast cancer and positive axillary lymph nodes if breast surgery is performed during the luteal phase (days 15-36) as compared with the follicular phase (days 0-14) of the menstrual cycle.[219,220,221][Level of evidence: 1iiA] Several other studies, however, have failed to support this finding or have found opposite results.[223,224,225,226][Level of evidence: 1iiA] Because of the inconsistent findings of these studies, it would be premature to mandate a modification in the scheduling of breast cancer operations according to the patient's menstrual cycle. A prospectively controlled trial (UCLA-9810046) has been completed but is not yet analyzed.
Adjuvant chemotherapy is associated with several well-characterized toxic effects that vary according to the individual drugs used in each regimen. Common toxic effects include nausea and vomiting, myelosuppression, alopecia, and mucositis. Less common, but serious, toxic effects include heart failure (if an anthracycline is used), thromboembolic events, and premature menopause. (Refer to the PDQ summary on Nausea and Vomiting; for information on mucositis, refer to the PDQ summary on Oral Complications of Chemotherapy and Head/Neck Radiation; and for information on symptoms associated with premature menopause, refer to the PDQ summary on Fever, Sweats, and Hot Flashes.)
Cognitive impairment has been reported to occur after the administration of some chemotherapy regimens. However, data on this topic from prospective randomized studies are lacking. (Refer to the PDQ summary on Cognitive Disorders and Delirium for more information.)
The EBCTCG meta-analysis revealed that women who received adjuvant combination chemotherapy did have a 20% (standard deviation = 10) reduction in the annual odds of developing contralateral breast cancer. This small proportional reduction translated into an absolute benefit that was only marginally statistically significant, but it indicates that chemotherapy does not increase the risk of contralateral disease. In addition, the analysis showed no statistically significant increase in deaths attributed to other cancers or to vascular causes among all women randomly assigned to receive chemotherapy. The use of anthracycline-containing regimens, however-particularly those containing an increased dose of cyclophosphamide-has been associated with a cumulative risk of developing acute leukemia of 0.2% to 1.7% at 5 years.[230,231] This risk increases to more than 4% in patients receiving high cumulative doses of both epirubicin (>720 mg/m2) and cyclophosphamide (>6,300 mg/m2).