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Is There a Role for Dose-Intensive Chemotherapy With Stem Cell Rescue in Breast Cancer?

Is There a Role for Dose-Intensive Chemotherapy With Stem Cell Rescue in Breast Cancer?

At first glance, high-dose chemotherapy for breast cancer makes sense. The disease is often sensitive to chemotherapy, potentially
curable, and highly prevalent, which means that even a modest benefit would be
tremendously important. Unfortunately, multiple clinical trials have failed to
demonstrate that high-dose therapy is more effective than other chemotherapeutic
approaches. Thus far, no prospective study has demonstrated a benefit based on
its planned primary objective and planned analysis, and none has shown a
survival advantage (see Table 1).[1-5]

Hence, the studies to date would be best used for hypothesis generation and
not for guidance in treating patients. On the other hand, this does not mean
that high-dose therapy could never be superior or that it could not be superior
in a selected cohort of patients. It does mean, however, that one should be
careful and conservative with regard to the further use and study of this
technique. Treatment outside of appropriate prospective studies cannot be
supported, and studies should be limited.

Parallel Thinking

It is instructive to compare our view of chemotherapy with our view of
surgery earlier in the past century. There are remarkable parallels in our
thinking on these two topics over time. "More" treatment—meaning
more extensive surgery—was presumed to be better than "less"
treatment, and some surgeons perfected and popularized extended radical
mastectomies with seemingly better outcomes compared to their own and
contemporaneous nonrandomized controls.

Later, multiple randomized trials finally convinced practitioners that this
widely accepted concept was incorrect and that as many patients could be cured
with "lesser" surgery as with the more extensive procedures. This
paved the way for the broad use of breast-conserving surgery, which may be
appropriate for the vast majority of patients with early-stage disease. Yet,
there are selected patients for whom mastectomy is still recommended, so we are
not yet convinced that breast conservation is always the appropriate option.

Almost the same story could be told regarding high-dose therapy. Knowing that
chemotherapy is effective, many of us were motivated to develop high-dose
regimens based on the hypothesis that "more" would be better.
Remarkable and important advances in supportive care resulted from the high-dose
experience with significant collateral benefit. But as with more extensive
surgery, we later showed that it was not clearly superior and, indeed, offers no
advantages in the majority of patients.

Perhaps the two stories now diverge in that we do not yet have any useful way
to predict which subset of patients might benefit from higher-than-standard-dose
treatment, just as we have no reliable way to predict which patients do not need
systemic chemotherapy at all. In contrast, we continue to rationally select some
patients for mastectomy instead of breast conservation. This is where our
efforts concerning high-dose therapy should be focused.

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