2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

UPDATE OF THE OXFORD OVERVIEW
Overview analyses looking at quantitative hormone receptor
levels or considering “2 � 2” analyses of ER by HER2 or ER
by grade may not be sufficiently “multiplexed” to figure out
which patients can avoid chemotherapy. A major limitation
with the present Overview is the lack of data on proliferation,
gene expression, modern immunohistochemical measurements
of receptors, quality controlled pathology
classification, and central marker review. Information on
these variables would, of course, have added value to the
EBCTCG processes and analyses, and some investigators
may claim that these shortcomings may explain some of the
results. Despite these shortcomings, the example of ER
values in the overall EBCTCG suggest very robust results in
relation to adjuvant tamoxifen, further supporting the validity
of the EBCTCG findings. 4
Additional methodologic details may be relevant. Several
studies that have identified selective benefit for chemotherapy
have centrally reanalyzed ER or HER2 data on some
patients, a detailed pathologic step not preformed in the
EBCTCG database. 8,10 Similarly, the Overview used a surrogate
strategy for high proliferation/higher OncotypeDx
scores by using grade as reported by local laboratories (in
particular, poorly differentiated cancers) that have not been
confirmed. Furthermore, the EBCTCG demonstration of
similar effects of chemotherapies, independent of studied
subgroups, could merely be a reflection of an inherent
common biology of breast cancer with a similar type of
Authors’ Disclosures of Potential Conflicts of Interest
Author
Employment or
Leadership
Positions
Consultant or
Advisory Role
Kathleen I. Pritchard GlaxoSmithKline;
Novartis; Ortho
Biotech; Pfizer;
Roche; Sanofi;
YM BioSciences
Jonas Bergh Affibody; Amgen;
AstraZeneca;
Bayer;
GlaxoSmithKline;
i3innovus; Onyx;
Pfizer; Sanofi;
Tapestry
Pharmaceuticals
Harold J. Burstein*
*No relevant relationships to disclose.
1. Early Breast Cancer Trialists’ Collaborative Group. Adjuvant polychemotherapy
in estrogen-receptor-poor breast cancer: Meta-analysis of individual
patient data from randomized trials. Lancet. 2008;371:29-40.
2. Early Breast Cancer Trialists’ Collaborative Group. Overview of the
randomized trials of radiotherapy in ductal carcinoma in situ (DCIS) of the
breast. J Natl Cancer Inst Monogr. 2010;41:162-177.
3. Early Breast Cancer Trialists’ Collaborative Group. Effect of radiotherapy
after breast-conserving surgery on 10-year recurrence and 15-year breast
cancer death: Meta-analysis of individual patient data for 10,801 women in 17
randomized trials. Lancet. 2011;378:1707-1716.
4. Early Breast Cancer Trialists’ Collaborative Group. Relevance of breast
cancer hormone receptors and other factors to the efficacy of adjuvant
tamoxifen: Patient-level meta-analysis of randomised trials. Lancet. 2011;
378:771-784.
5. Early Breast Cancer Trialists’ Collaborative Group. Comparisons between
different polychemotherapy regimens for early breast cancer: Metaanalyses
of long-term outcome among 100,000 women in 123 randomized
trials. Lancet. 2012;379:432-444.
sensitivity to the commonly used cytostatics. However, this
seems counterintuitive based on present extensive knowledge
of breast cancer biology in relation to outcome and
therapy strategies, but it has happened before in the era of
science that conclusions made with the best intentions have
required modification.
A possible explanation to the general findings of a similar
relative magnitude in anti–breast cancer effects in the
adjuvant setting by taxanes and anthracyclines could be
that all epithelial breast cancers seem to share so far
unidentified gene cassettes associated with a similar sensitivity
to chemotherapy. This could, to some extent, be
potentially substantiated by ongoing studies on human
breast cancer stem cells from primary cultures, which indicate
a common phenotype for most breast cancer stem cells
in relation to a specific receptor status, despite the fact that
cancers per se have different tumor and receptor characteristics
(Johan Hartman, Irma Fredriksson, Jonas Bergh,
verbal communications, March 1, 2012).
At its heart, the task of reconciling the invaluable data
from the ongoing Oxford Overview with the emerging data
from subset studies using novel markers remains the fundamental
challenge for adjuvant therapy for breast cancer.
Ongoing collaboration and research will be critical for helping
clinicians and patients understand these different but
important clinical datasets and solving the riddle of the
Overview paradox.
Stock
Ownership Honoraria
REFERENCES
AstraZeneca;
GlaxoSmithKline;
Novartis; Pfizer;
Roche; Sanofi
AstraZeneca;
Pfizer; Roche;
Sanofi
Research
Funding
Merck; Pfizer;
Roche
Expert
Testimony
AstraZeneca;
Novartis; Pfizer;
Sanofi
Other
Remuneration
AstraZeneca;
Roche
6. Goldhirsch A, Wood WC, Coates AS, et al. Strategies for subtypesdealing
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