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Surgeons Vol.2 Issue 3: Melvin
Silverstein, MD
Edited comments by Dr Silverstein
Increased detection of DCIS
In 1978, the American College of Surgeons conducted a survey
demonstrating that 200 out of 24,000 cases of breast cancer were
DCIS — less than one percent. The incidence of DCIS exploded
in the mammographic era. By screening women, we discovered microcalcifications
and other architectural distortions that we otherwise never would
have known were present. Some of those women would have developed
invasive breast cancer six to ten years later. Now, we intercede
in the neoplastic continuum five to ten years earlier. Today, DCIS
represents 21 percent of all new cancers. In 2003, we will detect
57,000 cases of DCIS and 211,000 cases of invasive breast cancer.
DCIS as more than a high-risk marker for breast
cancer
DCIS is the precursor lesion to invasive breast cancer. Roland
Holland, the renowned Dutch pathologist, examined 100 consecutive
invasive breast cancers, which he thoroughly sampled with multiple
slides for each. In 98 out of 100 cases, he found a DCIS component
in at least one of the slides. This is compelling evidence that
DCIS is a precursor lesion. It does not mean all DCIS will develop
into invasive breast cancer, rather all invasive breast cancers
were probably born from DCIS.
Our personal series has almost 1,100 patients with DCIS, of whom
10 percent have developed a contralateral breast cancer — approximately
50 percent are invasive and 50 percent are DCIS. That’s a
high number considering the median follow-up is only about eight
years in those patients, which translates into about a one percent
risk per year. This is consistent with the view that DCIS is also
a highrisk marker for contralateral breast cancer.
Clinical trials evaluating anastrozole for the
treatment of DCIS
NSABP-B-35 and IBIS-II are both evaluating anastrozole versus
tamoxifen for postmenopausal women with ER/PR-positive DCIS. Those
are exciting trials, and based on the existing data, I believe
these trials will eventually show anastrozole to be superior to
tamoxifen, with fewer side effects. In patients with invasive breast
cancer, my impression is that anastrozole has less toxicity, and
medical oncologists at the University of Southern California (USC)
view it as the adjuvant hormonal therapy of choice in postmenopausal
women with ERpositive invasive disease.
Which patients with DCIS need radiation therapy?
We know from Roland Holland’s work that DCIS tends to be
a segmental disease, and it usually involves only one ductal system.
It lends itself to local therapy, although complete excision is
difficult because the DCIS we treat today cannot be seen or felt.
Preoperatively, I map out the DCIS as well as I can with mammography
and MRI. I also use ultrasound, because sometimes we’ll find
a mass not visualized on X-ray. I use multiple wires to widely
excise the DCIS and submit all of the tissue sequentially. The
margins are analyzed and if they are clear by 10 millimeters or
more, we don’t treat those patients. I have a large number
of patients like this, and at 12 years of follow up, the local
recurrence rate is less than eight percent.
Radiation therapy in our series, as with the NSABP, reduces local
recurrence by about 50 percent, but that is a relative reduction.
If a patient has a 30 percent risk of local recurrence after surgery,
radiation will reduce it to 15 percent, and I recommend it. On
the other hand, if I widely excise a lesion and reduce the recurrence
risk to 6 to 8 percent, radiation therapy will decrease it to 3
to 4 percent, and then I don’t think it’s worth it.
Reducing the risk of recurrence with radiation therapy does not
translate into a survival benefit. If we look at the published
prospective randomized trials, there’s no difference in breast
cancer-specific or overall survival between women treated by excision
alone versus excision followed by radiation therapy. In my series,
I now have about 1,100 patients with DCIS who received three different
treatments. Although they’re selected, there’s no difference
whatsoever in terms of survival. The only difference is for local
recurrence. About one-half of local recurrences are invasive and
about 10 percent of those patients will die, so we’re talking
about small benefits. You would have to treat a few hundred patients
to save one life.
MammoSite® in the management of patients
with DCIS
I’ve been regarded as an anti-radiation therapy advocate
for years, but the new MammoSite® protocol for DCIS might change
my mind. I believe the MammoSite® will solve many of the problems
with traditional therapy, because treatment is only five days instead
of five or six weeks, it doesn’t irradiate the entire breast,
and it’s not expected to have the pulmonary or cardiac complications
we see with external beam therapy.
There’s a good rationale for brachytherapy — 80 or
90 percent of all local recurrences are at or near the primary
and are simply residual disease. In those cases, the patient doesn’t
need whole breast radiation. The MammoSite® radiates one centimeter
around the cavity to a dose of 34 Gy and then another centimeter
or two at a lower dose. I expect it will be more effective than
external beam therapy in treating the local margins and dealing
with 80 to 90 percent of recurrences. I also expect the MammoSite® will
reduce the need for re-excision.
Screening mammography in women younger than
50 years of age
I believe strongly in screening mammography and begin screening
women at the age of 40 — earlier if the woman is BRCA1/2-positive
or has a strong family history of breast cancer. We don’t
have good data for the benefit of screening mammography in women
younger than age 50. Breast cancer occurs less frequently in younger
women and because their breasts are denser, it’s more difficult
to detect subtle changes.
Michael Baum believes that the use of screening mammography in
women younger than age 50 does more harm than good. Clearly, when
you screen women, it will result in more biopsies being performed.
For every 100 biopsies performed, only 20 yield positive results
and not all are invasive cancer; many of the cases are DCIS. One
may argue we could wait to detect DCIS later, but I believe for
every DCIS cured, an invasive cancer may have been prevented. That
is the price we pay to detect cancer early.
I’m absolutely convinced by the data from Tabar and others
that patients benefit from screening. In our own series, when I
compare women with mammography-detected invasive cancers with women
who walked in with cancers we could palpate, women with mammography-detected
breast cancers have a 15-year survival of over 90 percent, but
in those with cancers we could palpate, it’s less than 70
percent.
 |
| Counterpoint by Michael Baum, MD, ChM,
FRCS, FRCR |
|
Mammography in women younger than 50 years of
age
The latest Canadian trial results published in the Annals of
Internal Medicine in September 2002 do not demonstrate an advantage
in breast cancer mortality. In fact, there is an excess mortality
from breast cancer in women younger than 50 years of age for the
first 10 years of the study. This excess mortality in the early
years has also been noticed in the overviews of the screening trials.
I had a patient with screening-detected DCIS. After a biopsy,
the patient was advised to have surgery, however, she chose not
to have treatment. She saw me six to nine months later with a breast
full of cancer. That is not the natural history of DCIS, but rather
the natural history of perturbed, incompletely excised DCIS. The
biological mechanism is perturbation of the tumor or its environment,
which induces angiogenesis.
Most in situ cancers are latent cancers, and angiogenesis is
the trigger from latency to invasion. Likewise, I believe most
patients with invasive cancer have metastases in dynamic equilibrium,
which may progress and become lifethreatening when the system is
perturbed and angiogenesis is induced. Women with latent breast
cancer or occult metastases are living close to a chaos boundary,
and we perturb the system at our peril.
Informed consent for mammography in women older
than 50 years of age
My argument against screening women older than 50 years of age
is not that it has no effect, but that we are disingenuous in the
way we invite women to be screened. I passionately believe that
women should make an informed choice.
With systemic therapy, we bend over backwards to inform women
of the absolute benefits. We agonize whether a two or three percent
improvement in five-year survival is worth the “side effects,” and
we counsel our patients this way. We tell women that screening
will save their lives and reduce their risk of dying by 20 percent.
In absolute terms, we have to screen 1,000 women for 10 years to
save one life — one in a thousand. If we told women truthfully, “If
I screen you for 10 years, you will have one in a thousand less
chance of breast cancer death, but a significant risk of overdiagnosis,
false alarms, health insurance issues, unnecessary biopsies and
detection of ductal carcinoma in situ, which never would have troubled
you,” many women would refuse it.
In the United States, I think there is a profit motive. In the
United Kingdom, it’s social engineering. I think it’s
almost fascistic to decide what is good for women and coerce them
to come forward for screening without telling them the whole truth.
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