Patients benefit from ease and success of
modern breast cancer screening.
By Paul Engstrom
Earlier this year Andrea Barish learned how new high-tech tools are supplementing an old one—
mammography, still the screening method of choice—in detecting and diagnosing breast cancer.
Barish, 45, strategic director of communications for Northern California at the American Cancer
Society’s office in Oakland, underwent surgery in 2006 for removal of an early-stage invasive ductal
carcinoma in her left breast, followed by radiation and chemotherapy. The centerpiece of her follow-up
screening in February 2007 in San Francisco was digital, rather than film, mamography.
Digital mammography captures X-ray images in computer code instead of on X-ray film, enabling the
operator to adjust an image’s magnification, orientation, brightness and contrast to get a clearer view.
Unlike its film counterpart, the digital device entails lower radiation doses and virtually no wait for results.
“It was very interesting,” Barish says. “One of the things
I wasn’t quite prepared for was that they were able to give
me my results immediately.” She says not having to wait
anxiously for the film to be developed and read, and for
the findings to arrive days later on a postcard, brought her
some comfort but also meant she might have to contend
with distressing news that same day. Fortunately, the digital
mammogram did not detect signs of recurrent disease.
"One of the things I wasn't quite prepared for [with digital mammography] was that they were able to give me my results
immediately."
—Andrea Barish
The goal of screening is not only to find more cancers,
but to have that result in
improved survival for those
patients. Experts attribute
declines in breast cancer
deaths since 1990 to a combination
of early detection, with
the aid of tools like mammography,
and better therapies.
Statistics show mammograms
reduce such deaths by 20 to
35 percent in women between
ages 50 and 69, and by about
20 percent in women in their
40s. The American Cancer
Society now recommends
women undergo annual mammograms beginning at age 40
(the previous recommendation was every year or two for
ages 40 to 49) because earlier detection means a greater
chance of survival and more treatment options.
Clinicians are turning to state-of-the-art tools and
techniques, or combinations of them, to supplement
mammography and in some cases ease the impact of procedures
on patients. Although mammography remains the
only widely accepted (and most widely available) imaging method for routine breast cancer screening, various other
techniques may be used.
Digital Mammography
In addition to improving the quality of images the
radiologist sees and, as Barish discovered, speeding the
whole screening process, a study of about 50,000 women,
published in the New England Journal of Medicine in 2005,
suggested another potential advantage. Although overall
diagnostic accuracy of the two screening techniques was
similar, investigators reported that digital mammography
was more accurate than film mammography as a screening
tool for women with dense breasts, those younger
than 50 and who are premenopausal or perimenopausal.
Often‚ digital mammography is paired with sophisticated
software that can bring suspicious areas to the
radiologist’s attention. CAD‚ or computer-aided detection‚
is pattern-recognition software that can flag suspicious
lesions the radiologist may have overlooked and
that might warrant examination. It leverages the notion
that computer knowledge tends to be more consistent
than human knowledge in analyzing an image, says Gary
Whitman, MD, a radiologist at M.D. Anderson Cancer
Center in Houston.
“Maybe one day the radiologist is distracted or just not
focusing, and performance drops off a bit,” he says. “With
the computer, performance should be relatively constant.”
However, a new study published in NEJM in April found
that use of CAD did not clearly improve the detection of
breast cancer and may instead make readings less accurate,
leading to a higher number of false positives.
Minimally Invasive Biopsy
This technique involves removing a tissue sample with
a hollow needle instead of surgically, which entails greater
risk, discomfort and scarring. Minimally invasive biopsies,
such as fine needle aspiration (FNA), core biopsy
and vacuum-assisted biopsy, are commonly used and have
the potential to spare up to 80 percent of women who
otherwise might undergo open breast biopsy.
Danene Birtell has seen the payoffs of minimally invasive
biopsy firsthand. Daunting aspects of two surgeries
back in 1998 and 2001—preoperative blood work,
general anesthesia, scalpel cuts and sutures—to excise a
suspicious growth from her right and then her left breast
after core biopsies seem almost quaint now.
That’s because in 2006, the 31-year-old veterinary
nurse from Yardley, Pennsylvania, had a third growth
removed as an outpatient by means of a vacuum-assisted
biopsy. After a small incision and under local anesthesia,
the doctor pinpointed and removed the growth from surrounding
tissue through a pencil-sized needle. Doctors
can withdraw larger segments of tissue with vacuumassisted
biopsy than with FNA or core biopsy.
In all three instances, the growths proved to be benign
fibroadenomas. But the third time, Birtell could watch
the entire procedure on a nearby monitor while interacting
with the surgeon. Closure of the quarter-inch surgical
cut with tape strips rather than traditional sutures
contributed to her quick recovery, despite some minor
bruising. She even attended kick-boxing camp in Oregon
the following week.
“I think the development of this procedure is just great,” Birtell says. “The less [surgery], the better.”
Ultrasound
Echoes from sound waves bounce off tissues and organs,
producing distinct images. Ultrasound, or sonogram, can
distinguish between solid masses and fluid-filled cysts,
assess lumps that are difficult to see or inconclusive on a
mammogram, or guide a surgeon’s instrument to a precise
location during biopsy.
“The quality of the ultrasound image has improved,
which makes it easier to put the [biopsy] needle in the
right place and to see lumps that are a bit smaller than we
used to be able to see—and see them accurately,” says Jack
Meyer, MD, a radiologist at Dana-Farber Cancer Institute
and Brigham and Women’s Hospital in Boston. Studies
are ongoing to see if ultrasound can be useful as a screening
tool in addition to simply focusing on abnormalities
picked up on physical examination or mammogram.
"What's been exciting is that we’ve discovered MRI can detect cancers invisible
on mammography, on ultrasound and on clinical breast exam."
—Constance Lehman,
MD, PhD
Magnetic Resonance Imaging
A magnet linked to a computer yields detailed, threedimensional
images of tissue—enhanced by an intravenous
contrast agent—without the radiation exposure that comes with X-ray mammography.
MRI is versatile. Among other uses, it can investigate
suspicious findings on mammogram images, which are
only two-dimensional; investigate abnormal tissue that is
felt but not visible on a mammogram or ultrasound; assess
the extent of diagnosed disease; and potentially find cancer
that mammography overlooked in the dense breasts of
younger women, especially those at high genetic risk.
“What’s been exciting is that we’ve discovered MRI can
detect cancers invisible on mammography, on ultrasound
and on clinical breast exam,” says Constance Lehman,
MD, PhD, director of breast imaging at the Seattle
Cancer Care Alliance. Breast MRI remains a difficult
examination to perform and interpret well, say experts,
and requires highly experienced breast MRI clinicians. In
addition, MRI is currently used primarily in very high-risk
situations, such as individuals with a genetic predisposition—specifically, mutations in the BRCA1 or BRCA2
genes.
The American Cancer Society published new guidelines
in March for breast screening MRI to include women
with a BRCA1 or BRCA2 mutation (the inherited gene
mutations that carry a high risk of breast cancer), a strong family history of breast or ovarian cancer, a 20
percent or greater lifetime risk of breast cancer
and who had radiation therapy to the chest for
treatment of Hodgkin’s disease.
Positron Emission Tomography
PET scans are more accurate in finding large,
aggressive growths. Since tumor tissue uses more
glucose than normal breast tissue‚ PET scanning
detects tumors by determining sugar absorption
in breast tissue. Clinicians may also use PET
to gauge the extent of disease—though the test
may not be completely accurate—and to monitor
tumor shrinkage after treatment.
What It All Means
At first glance, breast cancer may appear no
match against this impressive arsenal. But, as
clinicians are quick to point out, no individual
tool is appropriate for detecting all types of breast
cancer. And each has strengths and weaknesses—
including high cost and, in some instances, false
positives (results that initially suggest cancer but
in fact are benign, leading to needless anxiety for
patients and unnecessary surgery).
Take ultrasound, for example. While ultrasound
is “very powerful,” its sensitivity—the
proportion of true positives it finds—in detecting
breast cancer isn’t as high as with MRI, says Dr.
Lehman. High sensitivity may mean MRI is particularly
appropriate for high-risk women who
are genetically predisposed for breast cancer.
Investigators reported in NEJM in March that
MRIs in women who were diagnosed with cancer
in one breast detected more than 90 percent of
cancers in the other breast that were missed by
mammography and clinical exam at initial diagnosis.“We found that when we add screening
MRI to the screening mammography program,
we can significantly increase the number of cancers
we find in this group,” says Dr. Lehman, who served as principal investigator of the study. “It’s very exciting.”
The long-term hope of MRI’s ability to predict absence of a
tumor, say researchers, is to reduce the number of unnecessary
double, or bilateral, mastectomies at initial diagnosis. On the other
hand, the heightened sensitivity that makes MRI so valuable can
result in low specificity—a high rate of false positives. That may
mean MRI is less appropriate for lower-risk women, and experts
caution MRI should not be substituted for mammography.
The future holds promise for even newer technologies and for
refinement of those available now. For example, researchers hope biomarkers—molecular or cellular indicators of susceptibility to or
the presence of disease—will one day prove effective in detecting
breast cancer earlier, perhaps in combination with other screening
methods. BRCA1 and BRCA2 serve as biomarkers. The goal is to
identify other cancer susceptibility genes and blood-borne indicators
that would reliably aid detection in much larger populations,
says Jeffrey Marks, PhD, an associate professor of surgery at Duke
University Medical Center in Durham, North Carolina, who is
studying the molecular biology and genetics of breast cancer.
To be of clinical value, he says, new biomarkers must demonstrate
higher sensitivity and specificity than mammography—that is, generate
fewer false negatives and false positives—or somehow work in
tandem with mammography. Marks’s research focuses on creating a
so-called library of antibodies for breast cancer-secreted glycoproteins
that, in conjunction with mammography, could be applied to
help discriminate between cancerous and benign findings.
However, such breast cancer assays are years away, says Marks.“There’s no shortage of biomarkers that have been proposed, but
none of them have very good performance in real-life specimens.”
While biomarker research may not produce immediate screening
payoffs, it along with refined technologies like digital mammography
are expected to lead clinicians closer to a common goal:
earlier detection of breast cancer that translates into more patients
living longer.
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