Metronomic Schedule of Paclitaxel Is Effective in Hormone Receptor–Positive and Hormone Receptor–Negative Breast Cancer

J Clin Oncol. 2009 May 18.

Mehta RS, Jackson D, Schubbert T.

TO THE EDITOR: Hugh et al1 are to be lauded for their comprehensive
analysis of the benefit estimation of a docetaxel-based
regimen compared with the standard fluorouracil-based regimen
in various breast cancer subsets. After comparing trials in which
paclitaxel rather than docetaxel was used, they suggest that the
benefit seen with docetaxel in hormone receptor–positive subsets
may have resulted from either docetaxel being a more efficacious
taxane, or a docetaxel-specific schedule that was better than the schedule
of paclitaxel once every 3 weeks. However, they do not expand on
paclitaxel scheduling; we believe this is a crucial omission in their
discussion. In fact, missing from their discussion is a major phase III
randomized trial that clearly established the superiority of paclitaxel
once per week over paclitaxel once every 3 weeks,2 whereas the overall
survival benefit of docetaxel once every 3 weeks over paclitaxel once
every 3 weeks has yet to be demonstrated. In fact, the superiority of
paclitaxel once per week over paclitaxel once every 3 weeks was first
predicted by Green et al,3

who showed paclitaxel once per week compared
with paclitaxel once every 3 weeks increased pathologic complete
response—a surrogate of disease-free and overall survival—in
the neoadjuvant setting in operable breast cancer, in both hormone
receptor–positiveandhormonereceptor–negative subsets. In the confirmatory
trial by Sparano et al,2 which evaluated the 5-year diseasefree
and overall survival end points and compared the two taxanes
and the two taxane schedules in a 2 x 2 factorial design, paclitaxel
once per week compared with paclitaxel once every 3 weeks significantly
improved 5-year progression-free survival in hormone
receptor–negative breast cancer, including triple-negative and human
epidermal growth factor receptor 2 (HER2) –positive subsets of
breast cancer, and hormone receptor–positive breast cancer, which
combines luminal-A and luminal-B subtypes of breast cancer. This
was seen despite the fact that patients with HER2-positive breast
cancer (including luminal-B breast cancer, an HER2-positive subtype)
were preferentially enrolled onto the alternate trastuzumab trials;
these patients were more likely to have chemotherapy-sensitive
disease and therefore more likely to benefit from weekly paclitaxel. It is
likely that the small subgroup of patients with hormone receptor–
positive breast cancer with low Ki-67 proliferation index that did not
benefit from a docetaxel-based regimen in the study by Hugh et al1
may not have benefited from paclitaxel once per week either. This
subgroup may be akin to the group identified by multigene assay
that did not benefit from first-generation chemotherapy regimens.
Until this subset of patients who will not benefit from paclitaxel
once per week is identified, weekly paclitaxel after anthracyclines
should be standard in all subsets of breast cancer, including triplenegative,
hormone receptor–positive (estrogen receptor–positive
and/or progesterone receptor–positive and either HER2-positive
and/or Ki67high breast cancer), HER2–positive, and luminal-A (estrogen
receptor–positive and/or progesterone receptor–positive but not
HER2-positive or Ki67high breast cancer)2-7 breast cancer. Moreover,
drug-specific optimal schedules of chemotherapy must always be
compared when comparing across trials and/or assessing outcome in
different subsets of breast cancer, because optimal schedules of various
chemotherapies are an important advancement in the treatment of
various malignancies, demonstrated convincingly in Ewing’s sarcoma
and ovarian cancer,8,9 in addition to breast cancer.