Timing of Primary and Adjuvant Therapy

Timing of Primary and Adjuvant Therapy

Postoperative adjuvant chemotherapy

The optimal time to initiate adjuvant therapy is uncertain. A single study that addressed the use of perioperative adjuvant chemotherapy in node-positive patients showed no advantage in DFS when a single cycle of perioperative chemotherapy was given in addition to standard therapy initiated 4 weeks after surgery.[206] A single cycle of immediate postoperative chemotherapy alone was inferior.[207]

Preoperative adjuvant chemotherapy

A randomized clinical trial (NSABP-B-18) has been performed to evaluate preoperative chemotherapy in the management of patients with stage I or stage II breast cancer.[208] After preoperative therapy with four cycles of doxorubicin and cyclophosphamide, 80% of the assessable patients had a reduction in tumor size of at least 50%, and 36% of the patients had a complete clinical response. More patients treated with preoperative chemotherapy were able to have breast-conservation procedures as compared with those patients in the postoperative chemotherapy group (68% vs. 60%). Twenty-seven percent of the women in the preoperative therapy group for whom a mastectomy had been planned prior to being randomly assigned underwent a lumpectomy. No statistically significant difference existed, however, in DFS, distant DFS, or OS in the patients who received preoperative chemotherapy as compared with those who received postoperative chemotherapy.[208-210][Level of evidence: 1iiA]

An EORTC randomized trial (EORTC-10902) likewise demonstrated no improvement in DFS or OS, but showed an increased frequency of conservative surgery with the use of preoperative versus postoperative FEC chemotherapy.[211][Level of evidence: 1iiA] Preoperative chemotherapy may be beneficial in women who desire breast conservation surgery but who would otherwise not be considered candidates because of the size of their tumor. In a meta-analysis including all trials that compared the use of the same chemotherapy preoperatively and postoperatively, the use of preoperative chemotherapy was associated with a higher rate of local recurrence.[212] Although preoperative chemotherapy affects the results of SLN biopsy, one small study indicated that SLN biopsy technique was feasible in this setting.[213] Before SLN biopsy can replace complete axillary lymphadenectomy, randomized trials are needed to confirm that both procedures yield comparable survival rates.

In HER2-overexpressed disease, pilot studies have demonstrated remarkable clinical and pathologic responses when trastuzumab is given preoperatively in combination with chemotherapy.[214] A randomized study in patients with HER2-positive locally advanced or inflammatory breast cancers confirmed that the addition of neoadjuvant and adjuvant trastuzumab to neoadjuvant chemotherapy with sequential doxorubicin plus paclitaxel followed by CMF resulted not only in improved clinical responses (87% vs. 74%) and pathologic responses (38% vs. 19%) but also in the primary outcome: event-free survival (EFS).[215] This was defined as the time from random assignment to disease recurrence or progression—whether local, regional, distant, or contralateral—or death from any cause.

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