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I am sure that Dennis Slamon and his trastuzumab colleague
investigators struggled mightily when that fascinating therapeutic
agent first became available, and only through trial and
error did they eventually define a safe and effective protocol
for administration. Educational researchers (is that what I
am?) also need time to tailor their new “interventions,” and
this edition of Patterns of Care involves a modest but important
change in plan.
As with our first issue, we conducted random telephone surveys
of community-based oncologists throughout the country. Two
hundred brave souls were willing to give up 45 minutes of their
day for a modest honorarium to provide us their perspectives,
opinions and treatment recommendations. The data are once
again presented in easy-to-read graphics.
The major change for this issue has to do with the commentary
supporting these graphics. Last time around we compiled
related quotes generated from the Breast Cancer Update audio
series. While these were an effective adjunct, we thought it
would be interesting to obtain specific perspectives on the
actual survey data. To this end, we recruited two renowned
research leaders and former Breast Cancer Update interviewees
— Drs Joyce O’Shaughnessy and Robert Carlson — to provide
their thoughts. To make this happen, I emailed Joyce and Bob
the results of the survey, which included a minimum of 100
physician responses to each question. We then chatted about
the data in a series of in-depth teleconferences. Edited smatterings
of these conversations are interspersed throughout this
monograph.
With regard to the survey, we really don’t know if what the
participating physicians say they do is, in fact, what they
actually do in clinical practice. We expect and hope that these
responses are closely correlated with intended treatment plans.
Note that oncologist responses are totally anonymous. We do
hope to expand our quest to define how patients are treated and
perhaps someday include data documented by medical records.
Meanwhile, we see many new and interesting trends in the
current survey data, including the following:
- Adjuvant taxane-containing regimens — either dose
dense AC
 paclitaxel, TAC, or AC docetaxel — have
quickly become standard of care for women with nodepositive
or high-risk node-negative tumors. This reflects a
similar consensus among clinical research leaders including
Drs O’Shaughnessy and Carlson.
- Aromatase inhibitors are now clearly preferred to tamoxifen
as adjuvant therapy for postmenopausal women with
ER-positive tumors. Anastrozole as up-front therapy,
exemestane and anastrozole for women who have had two
to three years of tamoxifen, and letrozole after five years of
tamoxifen are now common treatment approaches. Clearly,
2004 is “the year of the aromatase inhibitors.”
- Peter Ravdin has changed the clinical face of breast
cancer. Our survey clearly reflects that Peter’s Adjuvant!
model has permeated into oncologic practices nationwide.
Adjuvant! calculates the risk of relapse and mortality and
the impact of systemic agents and regimens. The incorporation
of this now validated model has changed the discussions
and decisions regarding adjuvant systemic therapy. In particular,
oncologists now use Adjuvant! to assist in assessing the
potential use of chemotherapy in borderline situations such
as elderly patients and those with node-negative disease.
Another valuable aspect of the Adjuvant! model is the way it
factors in competing causes of mortality in older patients.
- Systemic management of metastatic disease is variable. Dr Carlson noted that available clinical research data does
not clearly define preferred agents and regimens. In his
opinion, new studies should be conducted to address this
important issue. He also provides an intriguing comment
about his soon-to-be-presented (in San Antonio) paper on
LHRH agonist suppression plus anastrozole in premenopausal
women with ER-positive metastatic disease. “It is the
highest response rate to hormonal therapy that I have ever
seen,” he said.
Meanwhile, postmenopausal women with ER-positive disease
may be treated in just about any sequence that includes tamoxifen,
a steroidal and nonsteroidal aromatase inhibitor and
fulvestrant. A survey our group conducted involving more than
200 women with metastatic breast cancer suggests that perhaps
a third of patients prefer a monthly injection to a daily pill.
Fulvestrant is a particularly salient consideration in patients
already coming in monthly for bisphosphonate therapy.
Turning to the other key breast cancer molecular target,
the management of HER2-positive metastatic disease now
clearly includes trastuzumab from day one, although in the
uncommon situation of ER-positive, HER2-positive disease,
some physicians will utilize endocrine therapy prior to starting
trastuzumab. It is interesting that physicians in this survey
tend to use trastuzumab monotherapy a bit less than some of
the more experienced clinical researchers in the field. Many
research leaders, such as Melody Cobleigh, will not add chemotherapy
until they are sure that trastuzumab alone is not
controlling the tumor.
The next issue of our series will take a similar approach to
this one, and three new research leaders (Cliff Hudis, Debu
Tripathy and Gershon Locker) boldly comment on survey data
for the record. We shall then re-evaluate and move forward.
Your thoughts and suggestions are most welcome.
— Neil Love, MD
NLove@ResearchToPractice.net
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