[Lani]

Several recent studies, including that of Magnifico and
coworkers (1) in this issue of Clinical Cancer Research , suggest
that the remarkable clinical efficacy of trastuzumab may relate
to its ability to target breast cancer stem cells. These studies have
important clinical implications for patient selection as well as
for the development of new therapeutic strategies to target the
cancer stem cell population.
The HER2 gene is amplified in approximately 20% of human
breast cancers in which it is associated with aggressive disease
and early development of metastasis (2). One of the greatest
advancements in the treatment of breast cancer has been the
development of trastuzumab to target HER2-positive disease.
When added to chemotherapy, trastuzumab significantly
increases both disease-free survival as well as overall survival
in women with metastatic breast cancer. The clinical utility of
trastuzumab has been even more remarkable in the adjuvant
setting. The addition of trastuzumab to cytotoxic chemotherapy
has reduced the recurrence rate by ~50% in women whose
breast cancers display HER2 amplification. Furthermore, the
natural history of HER2-amplified breast cancer as well as the
flattening survival curves suggest that a considerable proportion
of these patients may be cured of their disease. Although it
is clear that HER2 plays an important role in breast tumori-
genesis, the molecular mechanisms which account for the
clinical benefit of HER2 inhibition remain unknown.

*Max Wicha is one of the major proponents of the breast cancer stem cell
theory, head of Oncology at the University of Michigan and has been stubborn in his quest to find ways to kill these slowly growing "roots" of the weed which he believes responsible for cancer's recurrence and spread

the article he is commenting on involves her2, stem cells and notch signalling--somewhat technical but very promising