Over the past 2 decades, two major trends in the treatment of breast cancerbreast-conserving therapy and neoadjuvant (or preoperative) chemotherapyhave converged to stimulate interest in the use of neoadjuvant chemotherapy to facilitate breast conservation in women presenting with large tumors. After being established as the treatment of choice for locally advanced or inoperable breast cancer, theoretical considerations and the desire to extend breast-conserving therapy to more patients with large tumors have resulted in an increase in the use of neoadjuvant chemotherapy in operable patients. Drs. Green and Hortobagyi have provided us with a comprehensive review of the background and the current state of neoadjuvant chemotherapy for breast cancer.
As the authors explain, several early nonrandomized and randomized trials were interpreted as indicating a survival advantage for neoadjuvant chemotherapy over the standard adjuvant approach. Nonrandomized trials reaching this conclusion have little weight, and even some of the randomized trials of neoadjuvant therapy were seriously flawed, making this conclusion questionable.
For example, in two large European trials, a significant proportion of patients in the adjuvant group received no chemotherapy at all, whereas all patients in the neoadjuvant group received systemic treatment.[1,2] By the current standard of adjuvant treatment, patients with tumors > 3 cm in diameter would receive chemotherapy regardless of nodal status. More importantly, this selective use of chemotherapy in the adjuvant arms of these studies results in unbalanced treatment, invalidating conclusions about the preferred sequence of therapy. In addition, as Green and Hortobagyi pointed out, with longer follow-up, the survival advantage attributed to preoperative chemotherapy disappeared.[3,4]
The National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol B-18 demonstrated the equivalence of neoadjuvant chemotherapy in terms of survival, as well as an increase in the use of breast-conserving therapy.[5,6] Thus, there are adequate data to support the use of this approach in women with large tumors, to make breast-conserving therapy feasible.
The difficulty in assessing the extent of residual tumor after chemotherapy, discussed briefly in this review, raises a number of issues relevant to the surgical management of women whose tumors have been "shrunk" by neoadjuvant chemotherapy. As the authors point out, no single test or combination of tests has been completely reliable in delineating whether and where viable tumor remains in the breast. This explains why attempts to omit surgical excision of the primary tumor site, even in highly selected patients with an apparent complete response, have often led to unacceptably high local recurrence rates.[3,4,7,8] In NSABP trial B-18, in which surgical excision with a negative margin was required by protocol, early results indicated a higher rate of local recurrence among women who became candidates for breast-conserving therapy as a result of preoperative chemotherapy.