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Neoadjuvant Chemotherapy for Operable Breast Cancer

Neoadjuvant Chemotherapy for Operable Breast Cancer

Over the past 2 decades, two major trends in the
treatment of breast cancer—breast-conserving therapy and neoadjuvant (or
preoperative) chemotherapy—have 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.

Flawed Data

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.

Residual Disease

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.[6]

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